Dynamic HypA zinc site is essential for acid viability and proper urease maturation in Helicobacter pylori.

PubMed

Johnson, Ryan C; Hu, Heidi Q; Merrell, D Scott; Maroney, Michael J

2015-04-01

Helicobacter pylori requires urease activity in order to survive in the acid environment of the human stomach. Urease is regulated in part by nickelation, a process that requires the HypA protein, which is a putative nickel metallochaperone that is generally associated with hydrogenase maturation. However, in H. pylori, HypA plays a dual role. In addition to an N-terminal nickel binding site, HypA proteins also contain a structural zinc site that is coordinated by two rigorously conserved CXXC sequences, which in H. pylori are flanked by His residues. These structural Zn sites are known to be dynamic, converting from Zn(Cys)4 centers at pH 7.2 to Zn(Cys)2(His)2 centers at pH 6.3 in the presence of Ni(ii) ions. In this study, mutant strains of H. pylori that express zinc site variants of the HypA protein are used to show that the structural changes in the zinc site are important for the acid viability of the bacterium, and that a reduction in acid viability in these variants can be traced in large measure to deficient urease activity. This in turn leads to a model that connects the Zn(Cys)4 coordination to urease maturation.

Binding Site Configurations Probe the Structure and Dynamics of the Zinc Finger of NEMO (NF-κB Essential Modulator).

PubMed

Godwin, Ryan C; Melvin, Ryan L; Gmeiner, William H; Salsbury, Freddie R

2017-01-31

Zinc-finger proteins are regulators of critical signaling pathways for various cellular functions, including apoptosis and oncogenesis. Here, we investigate how binding site protonation states and zinc coordination influence protein structure, dynamics, and ultimately function, as these pivotal regulatory proteins are increasingly important for protein engineering and therapeutic discovery. To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), as well as the role of zinc, we present results of 20 μs molecular dynamics trajectories, 5 μs for each of four active site configurations. Consistent with experimental evidence, the zinc ion is essential for mechanical stabilization of the functional, folded conformation. Hydrogen bond motifs are unique for deprotonated configurations yet overlap in protonated cases. Correlated motions and principal component analysis corroborate the similarity of the protonated configurations and highlight unique relationships of the zinc-bound configuration. We hypothesize a potential mechanism for zinc binding from results of the thiol configurations. The deprotonated, zinc-bound configuration alone predominantly maintains its tertiary structure throughout all 5 μs and alludes rare conformations potentially important for (im)proper zinc-finger-related protein-protein or protein-DNA interactions.

Effects of Zinc on Particulate Methane Monooxygenase Activity and Structure*

PubMed Central

Sirajuddin, Sarah; Barupala, Dulmini; Helling, Stefan; Marcus, Katrin; Stemmler, Timothy L.; Rosenzweig, Amy C.

2014-01-01

Particulate methane monooxygenase (pMMO) is a membrane-bound metalloenzyme that oxidizes methane to methanol in methanotrophic bacteria. Zinc is a known inhibitor of pMMO, but the details of zinc binding and the mechanism of inhibition are not understood. Metal binding and activity assays on membrane-bound pMMO from Methylococcus capsulatus (Bath) reveal that zinc inhibits pMMO at two sites that are distinct from the copper active site. The 2.6 Å resolution crystal structure of Methylocystis species strain Rockwell pMMO reveals two previously undetected bound lipids, and metal soaking experiments identify likely locations for the two zinc inhibition sites. The first is the crystallographic zinc site in the pmoC subunit, and zinc binding here leads to the ordering of 10 previously unobserved residues. A second zinc site is present on the cytoplasmic side of the pmoC subunit. Parallels between these results and zinc inhibition studies of several respiratory complexes suggest that zinc might inhibit proton transfer in pMMO. PMID:24942740

Selective electrodiffusion of zinc ions in a Zrt-, Irt-like protein, ZIPB

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, W.; Fu, D.; Chai, J.

2010-12-10

All living cells need zinc ions to support cell growth. Zrt-, Irt-like proteins (ZIPs) represent a major route for entry of zinc ions into cells, but how ZIPs promote zinc uptake has been unclear. Here we report the molecular characterization of ZIPB from Bordetella bronchiseptica, the first ZIP homolog to be purified and functionally reconstituted into proteoliposomes. Zinc flux through ZIPB was found to be nonsaturable and electrogenic, yielding membrane potentials as predicted by the Nernst equation. Conversely, membrane potentials drove zinc fluxes with a linear voltage-flux relationship. Direct measurements of metal uptake by inductively coupled plasma mass spectroscopy demonstratedmore » that ZIPB is selective for two group 12 transition metal ions, Zn{sup 2+} and Cd{sup 2+}, whereas rejecting transition metal ions in groups 7 through 11. Our results provide the molecular basis for cellular zinc acquisition by a zinc-selective channel that exploits in vivo zinc concentration gradients to move zinc ions into the cytoplasm.« less

Metal active site elasticity linked to activation of homocysteine in methionine synthases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koutmos, Markos; Pejchal, Robert; Bomer, Theresa M.

2008-04-02

Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry uponmore » binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.« less

Highly Reversible Zinc-ion Intercalation with Chevrel Phase Mo6S8 Nanocubes and Applications for Advanced Zinc-ion Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Yingwen; Luo, Langli; Zhong, Li

We demonstrate the application of the Chevrel phase Mo6S8 nanocubes as the anode material for rechargeable Zn-ion batteries. Mo6S8 can host Zn2+ ions reversibility both in aqueous and nonaqueous electrolytes with specific capacities around 90 mAh/g and exhibited remarkable intercalation kinetics as well as stability. Furthermore, we assembled full cells by integrating Mo6S8 anode with zinc-polyiodide (I-/I3-) based catholytes, and demonstrated that such fuel cells was also able to deliver outstanding rate performance and cyclic stability. This first demonstration of zinc intercalating anode could inspire the design of advanced Zn ion batteries.

The study of zinc ions binding to casein.

PubMed

Pomastowski, P; Sprynskyy, M; Buszewski, B

2014-08-01

The presented research was focused on physicochemical study of casein properties and the kinetics of zinc ions binding to the protein. Moreover, a fast and simple method of casein extraction from cow's milk has been proposed. Casein isoforms, zeta potential (ζ) and particle size of the separated caseins were characterized with the use of capillary electrophoresis, zeta potential analysis and field flow fractionation (FFF) technique, respectively. The kinetics of the metal-binding process was investigated in batch adsorption experiments. Intraparticle diffusion model, first-order and zero-order kinetic models were applied to test the kinetic experimental data. Analysis of changes in infrared bands registered for casein before and after zinc binding was also performed. The obtained results showed that the kinetic process of zinc binding to casein is not homogeneous but is expressed with an initial rapid stage with about 70% of zinc ions immobilized by casein and with a much slower second step. Maximum amount of bound zinc in the experimental conditions was 30.04mgZn/g casein. Copyright © 2014 Elsevier B.V. All rights reserved.

Single-Site Active Iron-Based Bifunctional Oxygen Catalyst for a Compressible and Rechargeable Zinc-Air Battery.

PubMed

Ma, Longtao; Chen, Shengmei; Pei, Zengxia; Huang, Yan; Liang, Guojin; Mo, Funian; Yang, Qi; Su, Jun; Gao, Yihua; Zapien, Juan Antonio; Zhi, Chunyi

2018-02-27

The exploitation of a high-efficient, low-cost, and stable non-noble-metal-based catalyst with oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) simultaneously, as air electrode material for a rechargeable zinc-air battery is significantly crucial. Meanwhile, the compressible flexibility of a battery is the prerequisite of wearable or/and portable electronics. Herein, we present a strategy via single-site dispersion of an Fe-N x species on a two-dimensional (2D) highly graphitic porous nitrogen-doped carbon layer to implement superior catalytic activity toward ORR/OER (with a half-wave potential of 0.86 V for ORR and an overpotential of 390 mV at 10 mA·cm -2 for OER) in an alkaline medium. Furthermore, an elastic polyacrylamide hydrogel based electrolyte with the capability to retain great elasticity even under a highly corrosive alkaline environment is utilized to develop a solid-state compressible and rechargeable zinc-air battery. The creatively developed battery has a low charge-discharge voltage gap (0.78 V at 5 mA·cm -2 ) and large power density (118 mW·cm -2 ). It could be compressed up to 54% strain and bent up to 90° without charge/discharge performance and output power degradation. Our results reveal that single-site dispersion of catalytic active sites on a porous support for a bifunctional oxygen catalyst as cathode integrating a specially designed elastic electrolyte is a feasible strategy for fabricating efficient compressible and rechargeable zinc-air batteries, which could enlighten the design and development of other functional electronic devices.

Free zinc ion and dissolved orthophosphate effects on phytoplankton from Coeur d'Alene Lake, Idaho

USGS Publications Warehouse

Kuwabara, J.S.; Topping, B.R.; Woods, P.F.; Carter, J.L.

2007-01-01

Coeur d'Alene Lake in northern Idaho is fed by two major rivers: the Coeur d'Alene River from the east and the St. Joe River from the south, with the Spokane River as its outlet to the north. This phosphorus-limited lake has been subjected to decades of mining (primarily for zinc and silver) and other anthropogenic inputs. A 32 full-factorial experimental design was used to examine the interactive effects of free (uncomplexed) zinc ion and dissolved-orthophosphate concentrations on phytoplankton that were isolated from two sites along a longitudinal zinc-concentration gradient in Coeur d'Alene Lake. The two sites displayed different dominant taxa. Chlorella minutissima, a dominant species near the southern St. Joe River inlet, exhibited greater sensitivity to free Zn ions than Asterionella formosa, collected nearer the Coeur d'Alene River mouth with elevated dissolved-zinc concentrations. Empirical phytoplankton-response models were generated to describe phytoplankton growth in response to remediation strategies in the surrounding watershed. If dissolved Zn can be reduced in the water column from >500 nM (i.e., current concentrations near and down stream of the Coeur d'Alene River plume) to <3 nM (i.e., concentrations near the southern St. Joe River inlet) such that the lake is truly phosphorus limited, management of phosphorus inputs by surrounding communities will ultimately determine the limnologic state of the lake.

Removal of lead and zinc ions from water by low cost adsorbents.

PubMed

Mishra, P C; Patel, R K

2009-08-30

In this study, activated carbon, kaolin, bentonite, blast furnace slag and fly ash were used as adsorbent with a particle size between 100 mesh and 200 mesh to remove the lead and zinc ions from water. The concentration of the solutions prepared was in the range of 50-100 mg/L for lead and zinc for single and binary systems which are diluted as required for batch experiments. The effect of contact time, pH and adsorbent dosage on removal of lead and zinc by adsorption was investigated. The equilibrium time was found to be 30 min for activated carbon and 3h for kaolin, bentonite, blast furnace slag and fly ash. The most effective pH value for lead and zinc removal was 6 for activated carbon. pH value did not effect lead and zinc removal significantly for other adsorbents. Adsorbent doses were varied from 5 g/L to 20 g/L for both lead and zinc solutions. An increase in adsorbent doses increases the percent removal of lead and zinc. A series of isotherm studies was undertaken and the data evaluated for compliance was found to match with the Langmuir and Freundlich isotherm models. To investigate the adsorption mechanism, the kinetic models were tested, and it follows second order kinetics. Kinetic studies reveals that blast furnace slag was not effective for lead and zinc removal. The bentonite and fly ash were effective for lead and zinc removal.

Heterogeneous Electrocatalyst with Molecular Cobalt Ions Serving as the Center of Active Sites.

PubMed

Wang, Jiong; Ge, Xiaoming; Liu, Zhaolin; Thia, Larissa; Yan, Ya; Xiao, Wei; Wang, Xin

2017-02-08

Molecular Co 2+ ions were grafted onto doped graphene in a coordination environment, resulting in the formation of molecularly well-defined, highly active electrocatalytic sites at a heterogeneous interface for the oxygen evolution reaction (OER). The S dopants of graphene are suggested to be one of the binding sites and to be responsible for improving the intrinsic activity of the Co sites. The turnover frequency of such Co sites is greater than that of many Co-based nanostructures and IrO 2 catalysts. Through a series of carefully designed experiments, the pathway for the evolution of the Co cation-based molecular catalyst for the OER was further demonstrated on such a single Co-ion site for the first time. The Co 2+ ions were successively oxidized to Co 3+ and Co 4+ states prior to the OER. The sequential oxidation was coupled with the transfer of different numbers of protons/hydroxides and generated an active Co 4+ ═O fragment. A side-on hydroperoxo ligand of the Co 4+ site is proposed as a key intermediate for the formation of dioxygen.

Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration.

PubMed

Zeng, Shemin; Hernández, Jasmine; Mullins, Robert F

2012-02-01

To investigate whether the benefit of Age-Related Eye Disease Study (AREDS) formula multivitamins and zinc in the progression of age-related macular degeneration (AMD) may occur through inhibiting inflammatory events in the choroid. Mouse C166 endothelial cells (ECs) and, for some experiments, human retinal pigment epithelium (RPE)-choroid organ cultures were treated with AREDS multivitamin solution (MVS) or ZnCl(2). The cytotoxicity of MVS was evaluated using a lactate dehydrogenase colorimetric assay. Cell motility was assessed using a scratch assay. Macrophage adhesion to EC monolayers or ICAM-1 protein was determined after MVS and zinc treatment and with or without lipopolysaccharide (LPS). Quantitative reverse transcription PCR and Western blot analysis were used to determine the effects of MVS on the expression of proinflammatory molecules in treated and untreated cells. AREDS MVS and zinc did not affect C166 EC viability until the 56th hour after treatment. Scratch assays showed partial inhibition of MVS and zinc on EC migration. In cell adhesion assays, MVS and zinc decreased the number of macrophages bound to EC and to ICAM-1 protein. Quantitative PCR showed that LPS increased the expression of ICAM-1 in both C166 and human RPE-choroid cultures, which was partially offset by MVS and zinc. MVS and zinc also mitigated LPS-induced ICAM-1 protein expression on Western blot analysis. Treatment with AREDS MVS and zinc may affect both angiogenesis and endothelial-macrophage interactions. These results suggest that AREDS vitamins and zinc ions may slow the progression of AMD, in part through the attenuation of EC activation.

The structural role of the zinc ion can be dispensable in prokaryotic zinc-finger domains

PubMed Central

Baglivo, Ilaria; Russo, Luigi; Esposito, Sabrina; Malgieri, Gaetano; Renda, Mario; Salluzzo, Antonio; Di Blasio, Benedetto; Isernia, Carla; Fattorusso, Roberto; Pedone, Paolo V.

2009-01-01

The recent characterization of the prokaryotic Cys2His2 zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified ≈300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys2His2 zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros56–142C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys2His2 coordination, in Ros homologues can either exploit a CysAspHis2 coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed. PMID:19369210

Zinc triggers microglial activation.

PubMed

Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

2008-05-28

Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

Effects of Antioxidant Components of AREDS Vitamins and Zinc Ions on Endothelial Cell Activation: Implications for Macular Degeneration

PubMed Central

Zeng, Shemin; Hernández, Jasmine

2012-01-01

Purpose. To investigate whether the benefit of Age-Related Eye Disease Study (AREDS) formula multivitamins and zinc in the progression of age-related macular degeneration (AMD) may occur through inhibiting inflammatory events in the choroid. Methods. Mouse C166 endothelial cells (ECs) and, for some experiments, human retinal pigment epithelium (RPE)–choroid organ cultures were treated with AREDS multivitamin solution (MVS) or ZnCl2. The cytotoxicity of MVS was evaluated using a lactate dehydrogenase colorimetric assay. Cell motility was assessed using a scratch assay. Macrophage adhesion to EC monolayers or ICAM-1 protein was determined after MVS and zinc treatment and with or without lipopolysaccharide (LPS). Quantitative reverse transcription PCR and Western blot analysis were used to determine the effects of MVS on the expression of proinflammatory molecules in treated and untreated cells. Results. AREDS MVS and zinc did not affect C166 EC viability until the 56th hour after treatment. Scratch assays showed partial inhibition of MVS and zinc on EC migration. In cell adhesion assays, MVS and zinc decreased the number of macrophages bound to EC and to ICAM-1 protein. Quantitative PCR showed that LPS increased the expression of ICAM-1 in both C166 and human RPE-choroid cultures, which was partially offset by MVS and zinc. MVS and zinc also mitigated LPS-induced ICAM-1 protein expression on Western blot analysis. Conclusions. Treatment with AREDS MVS and zinc may affect both angiogenesis and endothelial-macrophage interactions. These results suggest that AREDS vitamins and zinc ions may slow the progression of AMD, in part through the attenuation of EC activation. PMID:22247465

Analysis of zinc binding sites in protein crystal structures.

PubMed

Alberts, I L; Nadassy, K; Wodak, S J

1998-08-01

The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H-bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi-zinc sites. We find that H-bonding of oxygen containing residues (or water) to zinc bound histidines is almost universal in our dataset and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations.

Zinc triggers microglial activation

PubMed Central

Kauppinen, Tiina M.; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A.

2009-01-01

Microglia are resident immune cells of the central nervous system. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, “amoeboid” morphology and release matrix metalloproteinases, reactive oxygen species, and other pro-inflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here we show that zinc directly triggers microglial activation. Microglia transfected with an NF-kB reporter gene showed a several-fold increase in NF-kB activity in response to 30 μM zinc. Cultured mouse microglia exposed to 15 – 30 μM zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-κB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-κB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders. PMID:18509044

Synthesis and application of ion-imprinted polymer nanoparticles for the extraction and preconcentration of zinc ions.

PubMed

Roushani, Mahmoud; Abbasi, Shahryar; Khani, Hossein; Sahraei, Reza

2015-04-15

A new Zinc (II) ion-imprinted polymer (IIPs) nanoparticles was synthesised for the separation and recovery of trace Zn (II) ion from food and water sample. Zn (II) IIP was prepared by copolymerisation of methyl methacrylate (monomer) and ethylene glycol dimethacrylate (cross-linker) in the presence of Zn (II)-N,N'-o-phenylene bis (salicylideneimine) ternary complex wherein Zn (II) ion is the imprint ion and is used to form the imprinted polymer. Moreover, control polymer (NIP) particles were similarly prepared without the zinc (II) ions. The unleached and leached IIP particles were characterised by X-ray diffraction, Fourier transform infra-red spectroscopy and scanning electron microscopy. The preconcentration of Zn(2+) from aqueous solution was studied during rebinding with the leached IIP particles as a function of pH, the weight of the polymer material, the uptake and desorption times, the aqueous phase and the desorption volumes. Flame atomic absorption spectrometry was employed for determination of zinc in aqueous solution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immobilization of mercury and zinc in an alkali-activated slag matrix.

PubMed

Qian, Guangren; Sun, Darren Delai; Tay, Joo Hwa

2003-07-04

The behavior of heavy metals mercury and zinc immobilized in an alkali-activated slag (AAS) matrix has been evaluated using physical property tests, pore structure analysis and XRD, TG-DTG, FTIR and TCLP analysis. Low concentrations (0.5%) of mercury and zinc ions had only a slight affect on compressive strength, pore structure and hydration of AAS matrixes. The addition of 2% Hg ions to the AAS matrix resulted in a reduction in early compressive strength but no negative effects were noticed after 28 days of hydration. Meanwhile, 2% Hg ions can be effectively immobilized in the AAS matrix with the leachate meeting the USEPA TCLP mercury limit. For a 2% Zn-doped AAS matrix, the hydration of the AAS paste was greatly retarded and the zinc concentration in the leachate from this matrix was higher than 5mg/l even at 28 days. Based on these results, we conclude that the physical encapsulation and chemical fixation mechanisms were likely to be responsible for the immobilization of Hg ions in the AAS matrix while only chemical fixation mechanisms were responsible for the immobilization of Zn ions in the AAS matrix.

Solubilization of insoluble zinc compounds by Gluconacetobacter diazotrophicus and the detrimental action of zinc ion (Zn2+) and zinc chelates on root knot nematode Meloidogyne incognita.

PubMed

Saravanan, V S; Kalaiarasan, P; Madhaiyan, M; Thangaraju, M

2007-03-01

To examine the zinc (Zn) solubilization potential and nematicidal properties of Gluconacetobacter diazotrophicus. Atomic Absorption Spectrophotometer, Differential Pulse Polarography and Gas Chromatography Coupled Mass Spectrometry were used to estimate the total Zn and Zn(2+) ions and identify the organic acids present in the culture supernatants. The effect of culture filtrate of Zn-amended G. diazotrophicus PAl5 on Meloidogyne incognita in tomato was examined under gnotobiotic conditions. Gluconacetobacter diazotrophicus PAl5 effectively solubilized the Zn compounds tested and 5-ketogluconic acid was identified as the major organic acid aiding the solubilization of zinc oxide. The presence of Zn compounds in the culture filtrates of G. diazotrophicus enhanced the mortality and reduced the root penetration of M. incognita under in vitro conditions. 5-ketogluconic acid produced by G. diazotrophicus mediated the solubilization process and the available Zn(2+) ions enhanced the nematicidal activity of G. diazotrophicus against M. incognita. Zn solubilization and enhanced nematicidal activity of Zn-amended G. diazotrophicus provides the possibility of exploiting it as a plant growth promoting bacteria.

Relation of morphology of electrodeposited zinc to ion concentration profile

NASA Technical Reports Server (NTRS)

May, C. E.; Kautz, H. E.; Sabo, B. B.

1977-01-01

The morphology of electrodeposited zinc was studied with special attention to the ion concentration profile. The initial concentrations were 9M hydroxide ion and 1.21M zincate. Current densities were 6.4 to 64 mA/sq cm. Experiments were run with a horizontal cathode which was observed in situ using a microscope. The morphology of the zinc deposit was found to be a function of time as well as current density; roughly, the log of the transition time from mossy to large crystalline type deposit is inversely proportional to current density. Probe electrodes indicated that the electrolyte in the cathode chamber was mixed by self inducted convection. However, relatively large concentration gradients of the involved species existed across the boundary layer of the cathode. Analysis of the data suggests that the morphology converts from mossy to large crystalline when the hydroxide activity on the cathode surface exceeds about 12 M. Other experiments show that the pulse discharge technique had no effect on the morphology in the system where the bulk concentration of the electrolyte was kept homogeneous via self induced convection.

Removal of Zinc Form Carbonic Anhydrase: A Kinetics Experiment for Upper-Level Chemistry Laboratories

ERIC Educational Resources Information Center

Williams, Kathryn R.; Adhyaru, Bhavin

2004-01-01

An experiment on kinetics of deactivation of carbonic anhydrase by removal of zinc is demonstrated. Carbonic anhydrase, the enzyme that catalyzes the interconversion of carbon dioxide and bicarbonate, requires on Zn(II) ion in its active site, and removal of the zinc cofactor by complexion to another ligand leaves the apoenzyme, which is totally…

Copper and protons directly activate the zinc-activated channel.

PubMed

Trattnig, Sarah M; Gasiorek, Agnes; Deeb, Tarek Z; Ortiz, Eydith J Comenencia; Moss, Stephen J; Jensen, Anders A; Davies, Paul A

2016-03-01

The zinc-activated channel (ZAC) is a cationic ion channel belonging to the superfamily of Cys-loop receptors, which consists of pentameric ligand-gated ion channels. ZAC is the least understood member of this family so in the present study we sought to characterize the properties of this channel further. We demonstrate that not only zinc (Zn(2+)) but also copper (Cu(2+)) and protons (H(+)) are agonists of ZAC, displaying potencies and efficacies in the rank orders of H(+)>Cu(2+)>Zn(2+) and H(+)>Zn(2+)>Cu(2+), respectively. The responses elicited by Zn(2+), Cu(2+) and H(+) through ZAC are all characterized by low degrees of desensitization. In contrast, currents evoked by high concentrations of the three agonists comprise distinctly different activation and decay components, with transitions to and from an open state being significantly faster for H(+) than for the two metal ions. The permeabilities of ZAC for Na(+) and K(+) relative to Cs(+) are indistinguishable, whereas replacing all of extracellular Na(+) and K(+) with the divalent cations Ca(2+) or Mg(2+) results in complete elimination of Zn(2+)-activated currents at both negative and positive holding potentials. This indicates that ZAC is non-selectively permeable to monovalent cations, whereas Ca(2+) and Mg(2+) inhibit the channel. In conclusion, this is the first report of a Cys-loop receptor being gated by Zn(2+), Cu(2+) and H(+). ZAC could be an important mediator of some of the wide range of physiological functions regulated by or involving Zn(2+), Cu(2+) and H(+). Copyright © 2016 Elsevier Inc. All rights reserved.

On the active site of mononuclear B1 metallo β-lactamases: a computational study

NASA Astrophysics Data System (ADS)

Sgrignani, Jacopo; Magistrato, Alessandra; Dal Peraro, Matteo; Vila, Alejandro J.; Carloni, Paolo; Pierattelli, Roberta

2012-04-01

Metallo-β-lactamases (MβLs) are Zn(II)-based bacterial enzymes that hydrolyze β-lactam antibiotics, hampering their beneficial effects. In the most relevant subclass (B1), X-ray crystallography studies on the enzyme from Bacillus Cereus point to either two zinc ions in two metal sites (the so-called `3H' and `DCH' sites) or a single Zn(II) ion in the 3H site, where the ion is coordinated by Asp120, Cys221 and His263 residues. However, spectroscopic studies on the B1 enzyme from B. Cereus in the mono-zinc form suggested the presence of the Zn(II) ion also in the DCH site, where it is bound to an aspartate, a cysteine, a histidine and a water molecule. A structural model of this enzyme in its DCH mononuclear form, so far lacking, is therefore required for inhibitor design and mechanistic studies. By using force field based and mixed quantum-classical (QM/MM) molecular dynamics (MD) simulations of the protein in aqueous solution we constructed such structural model. The geometry and the H-bond network at the catalytic site of this model, in the free form and in complex with two common β-lactam drugs, is compared with experimental and theoretical findings of CphA and the recently solved crystal structure of new B2 MβL from Serratia fonticola (Sfh-I). These are MβLs from the B2 subclass, which features an experimentally well established mono-zinc form, in which the Zn(II) is located in the DCH site. From our simulations the ɛɛδ and δɛδ protomers emerge as possible DCH mono-zinc reactive species, giving a novel contribution to the discussion on the MβL reactivity and to the drug design process.

Zinc Biochemistry: From a Single Zinc Enzyme to a Key Element of Life12

PubMed Central

Maret, Wolfgang

2013-01-01

The nutritional essentiality of zinc for the growth of living organisms had been recognized long before zinc biochemistry began with the discovery of zinc in carbonic anhydrase in 1939. Painstaking analytical work then demonstrated the presence of zinc as a catalytic and structural cofactor in a few hundred enzymes. In the 1980s, the field again gained momentum with the new principle of “zinc finger” proteins, in which zinc has structural functions in domains that interact with other biomolecules. Advances in structural biology and a rapid increase in the availability of gene/protein databases now made it possible to predict zinc-binding sites from metal-binding motifs detected in sequences. This procedure resulted in the definition of zinc proteomes and the remarkable estimate that the human genome encodes ∼3000 zinc proteins. More recent developments focus on the regulatory functions of zinc(II) ions in intra- and intercellular information transfer and have tantalizing implications for yet additional functions of zinc in signal transduction and cellular control. At least three dozen proteins homeostatically control the vesicular storage and subcellular distribution of zinc and the concentrations of zinc(II) ions. Novel principles emerge from quantitative investigations on how strongly zinc interacts with proteins and how it is buffered to control the remarkably low cellular and subcellular concentrations of free zinc(II) ions. It is fair to conclude that the impact of zinc for health and disease will be at least as far-reaching as that of iron. PMID:23319127

The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases*

PubMed Central

Peterson, Ryan L.; Galaleldeen, Ahmad; Villarreal, Johanna; Taylor, Alexander B.; Cabelli, Diane E.; Hart, P. John; Culotta, Valeria C.

2016-01-01

In eukaryotes the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. Recently, we reported that the fungal pathogen Candida albicans expresses a novel copper-only SOD, known as SOD5, that lacks the zinc cofactor and electrostatic loop (ESL) domain of Cu/Zn-SODs for substrate guidance. Despite these abnormalities, C. albicans SOD5 can disproportionate superoxide at rates limited only by diffusion. Here we demonstrate that this curious copper-only SOD occurs throughout the fungal kingdom as well as in phylogenetically distant oomycetes or “pseudofungi” species. It is the only form of extracellular SOD in fungi and oomycetes, in stark contrast to the extracellular Cu/Zn-SODs of plants and animals. Through structural biology and biochemical approaches we demonstrate that these copper-only SODs have evolved with a specialized active site consisting of two highly conserved residues equivalent to SOD5 Glu-110 and Asp-113. The equivalent positions are zinc binding ligands in Cu/Zn-SODs and have evolved in copper-only SODs to control catalysis and copper binding in lieu of zinc and the ESL. Similar to the zinc ion in Cu/Zn-SODs, SOD5 Glu-110 helps orient a key copper-coordinating histidine and extends the pH range of enzyme catalysis. SOD5 Asp-113 connects to the active site in a manner similar to that of the ESL in Cu/Zn-SODs and assists in copper cofactor binding. Copper-only SODs are virulence factors for certain fungal pathogens; thus this unique active site may be a target for future anti-fungal strategies. PMID:27535222

Zinc binding groups for histone deacetylase inhibitors.

PubMed

Zhang, Lei; Zhang, Jian; Jiang, Qixiao; Zhang, Li; Song, Weiguo

2018-12-01

Zinc binding groups (ZBGs) play a crucial role in targeting histone deacetylase inhibitors (HDACIs) to the active site of histone deacetylases (HDACs), thus determining the potency of HDACIs. Due to the high affinity to the zinc ion, hydroxamic acid is the most commonly used ZBG in the structure of HDACs. An alternative ZBG is benzamide group, which features excellent inhibitory selectivity for class I HDACs. Various ZBGs have been designed and tested to improve the activity and selectivity of HDACIs, and to overcome the pharmacokinetic limitations of current HDACIs. Herein, different kinds of ZBGs are reviewed and their features have been discussed for further design of HDACIs.

Crystal structure of Helicobacter pylori neutrophil-activating protein with a di-nuclear ferroxidase center in a zinc or cadmium-bound form

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yokoyama, Hideshi, E-mail: h-yokoya@u-shizuoka-ken.ac.jp; Tsuruta, Osamu; Akao, Naoya

2012-06-15

Highlights: Black-Right-Pointing-Pointer Structures of a metal-bound Helicobacter pylori neutrophil-activating protein were determined. Black-Right-Pointing-Pointer Two zinc ions were tetrahedrally coordinated by ferroxidase center (FOC) residues. Black-Right-Pointing-Pointer Two cadmium ions were coordinated in a trigonal-bipyramidal and octahedral manner. Black-Right-Pointing-Pointer The second metal ion was more weakly coordinated than the first at the FOC. Black-Right-Pointing-Pointer A zinc ion was found in one negatively-charged pore suitable as an ion path. -- Abstract: Helicobacter pylori neutrophil-activating protein (HP-NAP) is a Dps-like iron storage protein forming a dodecameric shell, and promotes adhesion of neutrophils to endothelial cells. The crystal structure of HP-NAP in a Zn{sup 2+}-more » or Cd{sup 2+}-bound form reveals the binding of two zinc or two cadmium ions and their bridged water molecule at the ferroxidase center (FOC). The two zinc ions are coordinated in a tetrahedral manner to the conserved residues among HP-NAP and Dps proteins. The two cadmium ions are coordinated in a trigonal-bipyramidal and distorted octahedral manner. In both structures, the second ion is more weakly coordinated than the first. Another zinc ion is found inside of the negatively-charged threefold-related pore, which is suitable for metal ions to pass through.« less

Separating the Role of Protein Restraints and Local Metal-Site Interaction Chemistry in the Thermodynamics of a Zinc Finger Protein

PubMed Central

Dixit, Purushottam D.; Asthagiri, D.

2011-01-01

We express the effective Hamiltonian of an ion-binding site in a protein as a combination of the Hamiltonian of the ion-bound site in vacuum and the restraints of the protein on the site. The protein restraints are described by the quadratic elastic network model. The Hamiltonian of the ion-bound site in vacuum is approximated as a generalized Hessian around the minimum energy configuration. The resultant of the two quadratic Hamiltonians is cast into a pure quadratic form. In the canonical ensemble, the quadratic nature of the resultant Hamiltonian allows us to express analytically the excess free energy, enthalpy, and entropy of ion binding to the protein. The analytical expressions allow us to separate the roles of the dynamic restraints imposed by the protein on the binding site and the temperature-independent chemical effects in metal-ligand coordination. For the consensus zinc-finger peptide, relative to the aqueous phase, the calculated free energy of exchanging Zn2+ with Fe2+, Co2+, Ni2+, and Cd2+ are in agreement with experiments. The predicted excess enthalpy of ion exchange between Zn2+ and Co2+ also agrees with the available experimental estimate. The free energy of applying the protein restraints reveals that relative to Zn2+, the Co2+, and Cd2+-site clusters are more destabilized by the protein restraints. This leads to an experimentally testable hypothesis that a tetrahedral metal binding site with minimal protein restraints will be less selective for Zn2+ over Co2+ and Cd2+ compared to a zinc finger peptide. No appreciable change is expected for Fe2+ and Ni2+. The framework presented here may prove useful in protein engineering to tune metal selectivity. PMID:21943427

Determination of model parameters for zinc (II) ion biosorption onto powdered waste sludge (PWS) in a fed-batch system.

PubMed

Kargi, Fikret; Cikla, Sinem

2007-12-01

Biosorption of zinc (II) ions onto pre-treated powdered waste sludge (PWS) was investigated using a completely mixed tank operating in fed-batch mode instead of an adsorption column. Experiments with variable feed flow rate (0.05-0.5 L h(-1)), feed Zn(II) ion concentrations (37.5-275 mg L(-1)) and amount of adsorbent (1-6 g PWS) were performed using fed-batch operation at pH 5 and room temperature (20-25 degrees C). Break-through curves describing variations of aqueous (effluent) zinc ion concentrations with time were determined for different operating conditions. Percent zinc removal from the aqueous phase decreased, but the biosorbed (solid phase) zinc ion concentration increased with increasing feed flow rate and zinc concentration. A modified Bohart-Adams equation was used to determine the biosorption capacity of PWS (q'(s)) and the rate constant (K) for zinc ion biosorption. Biosorption capacity (q'(s)=57.7 g Zn kg(-1) PWS) of PWS in fed-batch operation was found to be comparable with powdered activated carbon (PAC) in column operations. However, the adsorption rate constant (K=9.17 m(3) kg(-1) h(-1)) in fed-batch operation was an order of magnitude larger than those obtained in adsorption columns because of elimination of mass transfer limitations encountered in the column operations. Therefore, a completely mixed tank operated in fed-batch mode was proven to be more advantageous as compared to adsorption columns due to better contact between the phases yielding faster adsorption rates.

Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV

PubMed Central

Houston, David M. J.; Bugert, Joachim J.; Denyer, Stephen P.

2017-01-01

Background There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions. Materials and methods PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit. Results Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1) a value comparable to aciclovir (EC50 = 0.18 μg mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution. Conclusions The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores. PMID:28665969

Equilibrium and thermodynamic analysis of zinc ions adsorption by olive oil mill solid residues.

PubMed

Hawari, A; Rawajfih, Z; Nsour, N

2009-09-15

This work investigated the equilibrium batch dynamics of using olive oil mill solid residues as an adsorbent for zinc removal from aqueous solutions. It was found that a sorbent concentration of 4 g L(-1) achieved the best removal percentage and the best sorbent capacity. Adsorption equilibrium was reached in 60 min for an initial zinc concentration of 0.25 mmol/L and 180 min for an initial zinc concentration of 1-3 mmol/L. A particle size of olive mill residue ranging from 0.85 to 1.18 mm was used in the study. It was found that the maximum adsorption capacity of zinc was at a pH value of 5.0. It was found that q(max) for zinc ions, was 5.63, 6.46, and 7.11 mg g(-1) at temperature values of 298, 308, and 328 K, respectively. The data pertaining to the sorption dependence upon metal ion concentration could be fitted to a Langmuir isotherm model. The second-order kinetic model provided the best correlation of the data. The change in entropy (DeltaS degrees ) and heat of adsorption (DeltaH degrees ) for zinc ions adsorption on olive mill solid residues were estimated as -1419 kJ kg(-1)K(-1) and 4.7 kJ kg(-1), respectively. The examined low-cost adsorbent could offer an effective way to decrease zinc ions concentration in wastewater.

Zinc induces exposure of hydrophobic sites in the C-terminal domain of gC1q-R/p33.

PubMed

Kumar, Rajeev; Peerschke, Ellinor I B; Ghebrehiwet, Berhane

2002-09-01

Endothelial cells and platelets are known to express gC1q-R on their surface. In addition to C1q, endothelial cell gC1q-R has been shown to bind high molecular weight kininogen (HK) and factor XII (FXII). However, unlike C1q, whose interaction with gC1q-R does not require divalent ions, the binding of HK to gC1q-R is absolutely dependent on the presence of zinc. However, the mechanism by which zinc modulates this interaction is not fully understood. To investigate the role of zinc, binding studies were done using the hydrophobic dye, bis-ANS. The fluorescence intensity of bis-ANS, greatly increases and the emission maximum is blue-shifted from 525 to 485nm upon binding to hydrophobic sites on proteins. In this report, we show that a blue-shift in emission maximum is also observed when bis-ANS binds to gC1q-R in the presence but not in the absence of zinc suggesting that zinc induces exposure of hydrophobic sites in the molecule. The binding of bis-ANS to gC1q-R is specific, dose-dependent, and reversible. In the presence of zinc, this binding is abrogated by monoclonal antibody 74.5.2 directed against gC1q-R residues 204-218. This segment of gC1q-R, which corresponds to the beta6 strand in the crystal structure, has been shown previously to be the binding site for HK. A similar trend in zinc-induced gC1q-R binding was also observed using the hydrophobic matrix octyl-Sepharose. Taken together, our data suggest that zinc can induce the exposure of hydrophobic sites in the C-terminal domain of gC1q-R involved in binding to HK/FXII.

The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases

DOE PAGES

Peterson, Ryan L.; Galaleldeen, Ahmad; Villarreal, Johanna; ...

2016-08-17

In eukaryotes the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. We reported that the fungal pathogen Candida albicans expresses a novel copper-only SOD, known as SOD5, that lacks the zinc cofactor and electrostatic loop (ESL) domain of Cu/Zn-SODs for substrate guidance. In spite of these abnormalities, C. albicans SOD5 can disproportionate superoxide at rates limited only by diffusion. Here we demonstrate that this curious copper-only SOD occurs throughout the fungal kingdom as well as in phylogenetically distant oomycetes or “pseudofungi” species. It is the only form ofmore » extracellular SOD in fungi and oomycetes, in stark contrast to the extracellular Cu/Zn-SODs of plants and animals. Through structural biology and biochemical approaches we demonstrate that these copper-only SODs have evolved with a specialized active site consisting of two highly conserved residues equivalent to SOD5 Glu-110 and Asp-113. The equivalent positions are zinc binding ligands in Cu/Zn-SODs and have evolved in copper-only SODs to control catalysis and copper binding in lieu of zinc and the ESL. Similar to the zinc ion in Cu/Zn-SODs, SOD5 Glu-110 helps orient a key copper-coordinating histidine and extends the pH range of enzyme catalysis. Furthermore, SOD5 Asp-113 connects to the active site in a manner similar to that of the ESL in Cu/Zn-SODs and assists in copper cofactor binding. Copper-only SODs are virulence factors for certain fungal pathogens; thus this unique active site may be a target for future anti-fungal strategies.« less

Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach.

PubMed

Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Gerdil, Adèle; Diemer, Hélène; Proamer, Fabienne; Collin-Faure, Véronique; Habert, Aurélie; Strub, Jean-Marc; Hanau, Daniel; Herlin, Nathalie; Carrière, Marie; Van Dorsselaer, Alain; Rabilloud, Thierry

2014-06-07

Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations.

Role of Conserved Glycine in Zinc-dependent Medium Chain Dehydrogenase/Reductase Superfamily*

PubMed Central

Tiwari, Manish Kumar; Singh, Raushan Kumar; Singh, Ranjitha; Jeya, Marimuthu; Zhao, Huimin; Lee, Jung-Kul

2012-01-01

The medium-chain dehydrogenase/reductase (MDR) superfamily consists of a large group of enzymes with a broad range of activities. Members of this superfamily are currently the subject of intensive investigation, but many aspects, including the zinc dependence of MDR superfamily proteins, have not yet have been adequately investigated. Using a density functional theory-based screening strategy, we have identified a strictly conserved glycine residue (Gly) in the zinc-dependent MDR superfamily. To elucidate the role of this conserved Gly in MDR, we carried out a comprehensive structural, functional, and computational analysis of four MDR enzymes through a series of studies including site-directed mutagenesis, isothermal titration calorimetry, electron paramagnetic resonance (EPR), quantum mechanics, and molecular mechanics analysis. Gly substitution by other amino acids posed a significant threat to the metal binding affinity and activity of MDR superfamily enzymes. Mutagenesis at the conserved Gly resulted in alterations in the coordination of the catalytic zinc ion, with concomitant changes in metal-ligand bond length, bond angle, and the affinity (Kd) toward the zinc ion. The Gly mutants also showed different spectroscopic properties in EPR compared with those of the wild type, indicating that the binding geometries of the zinc to the zinc binding ligands were changed by the mutation. The present results demonstrate that the conserved Gly in the GHE motif plays a role in maintaining the metal binding affinity and the electronic state of the catalytic zinc ion during catalysis of the MDR superfamily enzymes. PMID:22500022

The Crystal Structure of a Quercetin 2,3-Dioxygenase from Bacillus subtilis Suggests Modulation of Enzyme Activity by a Change in the Metal Ion at the Active Site(s)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gopal, B.; Madan, Lalima L.; Betz, Stephen F.

2010-11-10

Common structural motifs, such as the cupin domains, are found in enzymes performing different biochemical functions while retaining a similar active site configuration and structural scaffold. The soil bacterium Bacillus subtilis has 20 cupin genes (0.5% of the total genome) with up to 14% of its genes in the form of doublets, thus making it an attractive system for studying the effects of gene duplication. There are four bicupins in B. subtilis encoded by the genes yvrK, yoaN, yxaG, and ywfC. The gene products of yvrK and yoaN function as oxalate decarboxylases with a manganese ion at the active site(s),more » whereas YwfC is a bacitracin synthetase. Here we present the crystal structure of YxaG, a novel iron-containing quercetin 2,3-dioxygenase with one active site in each cupin domain. Yxag is a dimer, both in solution and in the crystal. The crystal structure shows that the coordination geometry of the Fe ion is different in the two active sites of YxaG. Replacement of the iron at the active site with other metal ions suggests modulation of enzymatic activity in accordance with the Irving-Williams observation on the stability of metal ion complexes. This observation, along with a comparison with the crystal structure of YvrK determined recently, has allowed for a detailed structure-function analysis of the active site, providing clues to the diversification of function in the bicupin family of proteins.« less

Combined copper/zinc attachment to prion protein

NASA Astrophysics Data System (ADS)

Hodak, Miroslav; Bernholc, Jerry

2013-03-01

Misfolding of prion protein (PrP) is responsible for diseases such as ``mad-cow disease'' in cattle and Creutzfeldt-Jacob in humans. Extensive experimental investigation has established that this protein strongly interacts with copper ions, and this ability has been linked to its still unknown function. Attachment of other metal ions (zinc, iron, manganese) have been demonstrated as well, but none of them could outcompete copper. Recent finding, however, indicates that at intermediate concentrations both copper and zinc ions can attach to the PrP at the octarepeat region, which contains high affinity metal binding sites. Based on this evidence, we have performed density functional theory simulations to investigate the combined Cu/Zn attachment. We consider all previously reported binding modes of copper at the octarepeat region and examine a possibility simultaneous Cu/Zn attachment. We find that this can indeed occur for only one of the known binding sites, when copper changes its coordination mode to allow for attachment of zinc ion. The implications of the simultaneous attachment on neural function remain to be explored.

Site preference for luminescent activator ions in doped fluoroperovskite RbZnF3.

PubMed

Saroj, Sanjay Kumar; Nagarajan, Rajamani

2018-08-05

With the dual objective of investigating the site preferences of larger sized activator ions and to append luminescence property to the perovskite structured RbZnF 3 , doping of manganese(II), cerium(III), europium(III) and terbium(III) ions (5 mol%) was carried out. Although cubic symmetry of RbZnF 3 was preserved for all the doped samples, site preference of rare-earth ions for the A-site Rb + leading to an inverse perovskite arrangement has been noticed from careful analysis of lattice parameters from refinement of powder X-ray diffraction data. Undoped RbZnF 3 exhibited rod-like morphology in the transmission electron microscopic image. In addition to an intense band around 230 nm assignable to the charge transfer from ZnF 3 - to Rb + , typical transitions of respective dopant ions were observed in their UV-visible spectra. The doped samples showed luminescence in blue, green and red regions and time decay experiments suggested uniform dispersion of them without any clustering effect. The lower phonon energy of RbZnF 3 matrix by virtue of the presence of heavier rubidium at the A-site together with its doping with rare-earth ions resulting in an inverse perovskite like arrangement could favour their utility in various practical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Zinc-ion-dependent acid phosphatase exhibits magnesium-ion-dependent myo-inositol-1-phosphatase activity.

PubMed

Fujimoto, S; Okano, I; Tanaka, Y; Sumida, Y; Tsuda, J; Kawakami, N; Shimohama, S

1996-06-01

We have purified bovine brain Zn(2+)-dependent acid phosphatase (Zn(2+)-APase), which requires Zn2+ ions to hydrolyze the substrate p-nitrophenyl phosphate (pNPP) in an acidic environment. The substrate specificity and metal requirement of Zn(2+)-APase at a physiological pH was also studied. The enzyme exhibited hydrolytic activity on myo-inositol-1- and -2-monophosphates, 2'-adenosine monophosphate, 2'-guanosine monophosphate, and the alpha- and beta-glycerophosphates, glucose-1-phosphate, and fructose-6-phosphate in 50 mM Tris-HCl buffer (pH 7.4) in the presence of Mg2+ ions, but not on pNPP and phosphotyrosine. Zn2+, Mn2+ and Co2+ ions were less effective for activation. Among the above substrates, myo-inositol-1-phosphate was the most susceptible to hydrolysis by the enzyme in the presence of 3 mM Mg2+ ions. The enzyme exhibited an optimum pH at around 8 for myo-inositol-1-phosphate in the presence of 3 mM Mg2+ ions. The Mg(2+)-dependent myo-inositol-1-phosphatase activity of the enzyme was significantly inhibited by Li+ ions. The Zn(2+)-dependent p-nitrophenyl phosphatase activity and Mg(2+)-dependent myo-inositol-1-phosphatase activity of the purified enzyme fraction exhibited similar behavior on Sephadex G-100 and Mono Q colomns. These findings suggest that Zn(2+)-APase also exhibits Mg(2+)-dependent myo-inositol-1-phosphatase activity under physiological conditions.

Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper

PubMed Central

Stafford, Sian L.; Bokil, Nilesh J.; Achard, Maud E. S.; Kapetanovic, Ronan; Schembri, Mark A.; McEwan, Alastair G.; Sweet, Matthew J.

2013-01-01

The immunomodulatory and antimicrobial properties of zinc and copper have long been appreciated. In addition, these metal ions are also essential for microbial growth and survival. This presents opportunities for the host to either harness their antimicrobial properties or limit their availability as defence strategies. Recent studies have shed some light on mechanisms by which copper and zinc regulation contribute to host defence, but there remain many unanswered questions at the cellular and molecular levels. Here we review the roles of these two metal ions in providing protection against infectious diseases in vivo, and in regulating innate immune responses. In particular, we focus on studies implicating zinc and copper in macrophage antimicrobial pathways, as well as the specific host genes encoding zinc transporters (SLC30A, SLC39A family members) and CTRs (copper transporters, ATP7 family members) that may contribute to pathogen control by these cells. PMID:23738776

Structure of the Zinc-Bound Amino-Terminal Domain of the NMDA Receptor NR2B Subunit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karakas, E.; Simorowski, N; Furukawa, H

2009-01-01

N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors (iGluRs) that mediate the majority of fast excitatory synaptic transmission in the mammalian brain. One of the hallmarks for the function of NMDA receptors is that their ion channel activity is allosterically regulated by binding of modulator compounds to the extracellular amino-terminal domain (ATD) distinct from the L-glutamate-binding domain. The molecular basis for the ATD-mediated allosteric regulation has been enigmatic because of a complete lack of structural information on NMDA receptor ATDs. Here, we report the crystal structures of ATD from the NR2B NMDA receptor subunit in the zinc-freemore » and zinc-bound states. The structures reveal the overall clamshell-like architecture distinct from the non-NMDA receptor ATDs and molecular determinants for the zinc-binding site, ion-binding sites, and the architecture of the putative phenylethanolamine-binding site.« less

Uncoupling metallonuclease metal ion binding sites via nudge mutagenesis.

PubMed

Papadakos, Grigorios A; Nastri, Horacio; Riggs, Paul; Dupureur, Cynthia M

2007-05-01

The hydrolysis of phosphodiester bonds by nucleases is critical to nucleic acid processing. Many nucleases utilize metal ion cofactors, and for a number of these enzymes two active-site metal ions have been detected. Testing proposed mechanistic roles for individual bound metal ions has been hampered by the similarity between the sites and cooperative behavior. In the homodimeric PvuII restriction endonuclease, the metal ion dependence of DNA binding is sigmoidal and consistent with two classes of coupled metal ion binding sites. We reasoned that a conservative active-site mutation would perturb the ligand field sufficiently to observe the titration of individual metal ion binding sites without significantly disturbing enzyme function. Indeed, mutation of a Tyr residue 5.5 A from both metal ions in the enzyme-substrate crystal structure (Y94F) renders the metal ion dependence of DNA binding biphasic: two classes of metal ion binding sites become distinct in the presence of DNA. The perturbation in metal ion coordination is supported by 1H-15N heteronuclear single quantum coherence spectra of enzyme-Ca(II) and enzyme-Ca(II)-DNA complexes. Metal ion binding by free Y94F is basically unperturbed: through multiple experiments with different metal ions, the data are consistent with two alkaline earth metal ion binding sites per subunit of low millimolar affinity, behavior which is very similar to that of the wild type. The results presented here indicate a role for the hydroxyl group of Tyr94 in the coupling of metal ion binding sites in the presence of DNA. Its removal causes the affinities for the two metal ion binding sites to be resolved in the presence of substrate. Such tuning of metal ion affinities will be invaluable to efforts to ascertain the contributions of individual bound metal ions to metallonuclease function.

Learning from oligosaccharide soaks of crystals of an AA13 lytic polysaccharide monooxygenase: crystal packing, ligand binding and active-site disorder.

PubMed

Frandsen, Kristian E H; Poulsen, Jens Christian Navarro; Tovborg, Morten; Johansen, Katja S; Lo Leggio, Leila

2017-01-01

Lytic polysaccharide monooxygenases (LPMOs) are a class of copper-dependent enzymes discovered within the last ten years. They oxidatively cleave polysaccharides (chitin, lignocellulose, hemicellulose and starch-derived), presumably making recalcitrant substrates accessible to glycoside hydrolases. Recently, the first crystal structure of an LPMO-substrate complex was reported, giving insights into the interaction of LPMOs with β-linked substrates (Frandsen et al., 2016). The LPMOs acting on α-linked glycosidic bonds (family AA13) display binding surfaces that are quite different from those of LPMOs that act on β-linked glycosidic bonds (families AA9-AA11), as revealed from the first determined structure (Lo Leggio et al., 2015), and thus presumably the AA13s interact with their substrate in a distinct fashion. Here, several new structures of the same AA13 enzyme, Aspergillus oryzae AA13, are presented. Crystals obtained in the presence of high zinc-ion concentrations were used, as they can be obtained more reproducibly than those used to refine the deposited copper-containing structure. One structure with an ordered zinc-bound active site was solved at 1.65 Å resolution, and three structures from crystals soaked with maltooligosaccharides in solutions devoid of zinc ions were solved at resolutions of up to 1.10 Å. Despite similar unit-cell parameters, small rearrangements in the crystal packing occur when the crystals are depleted of zinc ions, resulting in a more occluded substrate-binding surface. In two of the three structures maltooligosaccharide ligands are bound, but not at the active site. Two of the structures presented show a His-ligand conformation that is incompatible with metal-ion binding. In one of these structures this conformation is the principal one (80% occupancy), giving a rare atomic resolution view of a substantially misfolded enzyme that is presumably rendered inactive.

Binding of the Zn2+ ion to ferric uptake regulation protein from E. coli and the competition with Fe2+ binding: a molecular modeling study of the effect on DNA binding and conformational changes of Fur

NASA Astrophysics Data System (ADS)

Jabour, Salih; Hamed, Mazen Y.

2009-04-01

The three dimensional structure of Ferric uptake regulation protein dimer from E. coli, determined by molecular modeling, was docked on a DNA fragment (iron box) and Zn2+ ions were added in two steps. The first step involved the binding of one Zn2+ ion to what is known as the zinc site which consists of the residues Cys 92, Cys 95, Asp 137, Asp141, Arg139, Glu 140, His 145 and His 143 with an average metal-Nitrogen distance of 2.5 Å and metal-oxygen distance of 3.1-3.2 Å. The second Zn2+ ion is bound to the iron activating site formed from the residues Ile 50, His 71, Asn 72, Gly 97, Asp 105 and Ala 109. The binding of the second Zn2+ ion strengthened the binding of the first ion as indicated by the shortening of the zinc-residue distances. Fe2+, when added to the complex consisting of 2Zn2+/Fur dimer/DNA, replaced the Zn2+ ion in the zinc site and when a second Fe2+ was added, it replaced the second zinc ion in the iron activating site. The binding of both zinc and iron ions induced a similar change in Fur conformations, but shifted residues closer to DNA in a different manner. This is discussed along with a possible role for the Zn2+ ion in the Fur dimer binding of DNA in its repressor activity.

Zinc in Cellular Regulation: The Nature and Significance of "Zinc Signals".

PubMed

Maret, Wolfgang

2017-10-31

In the last decade, we witnessed discoveries that established Zn 2+ as a second major signalling metal ion in the transmission of information within cells and in communication between cells. Together with Ca 2+ and Mg 2+ , Zn 2+ covers biological regulation with redox-inert metal ions over many orders of magnitude in concentrations. The regulatory functions of zinc ions, together with their functions as a cofactor in about three thousand zinc metalloproteins, impact virtually all aspects of cell biology. This article attempts to define the regulatory functions of zinc ions, and focuses on the nature of zinc signals and zinc signalling in pathways where zinc ions are either extracellular stimuli or intracellular messengers. These pathways interact with Ca 2+ , redox, and phosphorylation signalling. The regulatory functions of zinc require a complex system of precise homeostatic control for transients, subcellular distribution and traffic, organellar homeostasis, and vesicular storage and exocytosis of zinc ions.

Two distinct modes of metal ion binding in the nuclease active site of a viral DNA-packaging terminase: insight into the two-metal-ion catalytic mechanism

PubMed Central

Zhao, Haiyan; Lin, Zihan; Lynn, Anna Y.; Varnado, Brittany; Beutler, John A.; Murelli, Ryan P.; Le Grice, Stuart F. J.; Tang, Liang

2015-01-01

Many dsDNA viruses encode DNA-packaging terminases, each containing a nuclease domain that resolves concatemeric DNA into genome-length units. Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, and share a two-metal-ion catalytic mechanism. Here we show that residue K428 of a bacteriophage terminase gp2 nuclease domain mediates binding of the metal cofactor Mg2+. A K428A mutation allows visualization, at high resolution, of a metal ion binding mode with a coupled-octahedral configuration at the active site, exhibiting an unusually short metal-metal distance of 2.42 Å. Such proximity of the two metal ions may play an essential role in catalysis by generating a highly positive electrostatic niche to enable formation of the negatively charged pentacovalent phosphate transition state, and provides the structural basis for distinguishing Mg2+ from Ca2+. Using a metal ion chelator β-thujaplicinol as a molecular probe, we observed a second mode of metal ion binding at the active site, mimicking the DNA binding state. Arrangement of the active site residues differs drastically from those in RNase H-like nucleases, suggesting a drifting of the active site configuration during evolution. The two distinct metal ion binding modes unveiled mechanistic details of the two-metal-ion catalysis at atomic resolution. PMID:26450964

[Effect of Cu2+ and Zn2+ ions in Ca-ATPase activity isolated from Pachymerus nucleorum (Fabricius) (Coleoptera: Chrysomelidae, Bruchinae) larvae].

PubMed

Dias, Decivaldo S; Coelho, Milton V

2007-01-01

ATPases, an important target of insecticides, are enzymes that hydrolyze ATP and use the energy released in that process to accomplish some type of cellular work. Pachymerus nucleorum (Fabricius) larvae possess an ATPase, that presents high Ca-ATPase activity, but no Mg-ATPase activity. In the present study, the effect of zinc and copper ions in the activity Ca-ATPase of that enzyme was tested. More than 90% of the Ca-ATPase activity was inhibited in 0.5 mM of copper ions or 0.25 mM of zinc ions. In the presence of EDTA, but not in the absence, the inhibition by zinc was reverted with the increase of calcium concentration. The inhibition by copper ions was not reverted in the presence or absence of EDTA. The Ca-ATPase was not inhibited by treatment of the ATPase fraction with copper, suggesting that the copper ion does not bind directly to the enzyme. The results suggest that zinc and copper ions form a complex with ATP and bind to the enzyme inhibiting its Ca-ATPase activity.

Molecular Characterization of a Chromosomal Determinant Conferring Resistance to Zinc and Cobalt Ions in Staphylococcus aureus

PubMed Central

Xiong, Anming; Jayaswal, Radheshyam K.

1998-01-01

A DNA fragment conferring resistance to zinc and cobalt ions was isolated from a genomic DNA library of Staphylococcus aureus RN450. The DNA sequence analysis revealed two consecutive open reading frames, designated zntR and zntA. The predicted ZntR and ZntA showed significant homology to members of ArsR and cation diffusion families, respectively. A mutant strain containing the null allele of zntA was more sensitive to zinc and cobalt ions than was the parent strain. The metal-sensitive phenotype of the mutant was complemented by a 2.9-kb DNA fragment containing zntR and zntA. An S. aureus strain harboring multiple copies of zntR and zntA showed an increased resistance to zinc. The resistance to zinc in the wild-type strain was inducible. Transcriptional analysis indicated that zntR and zntA genes were cotranscribed. The zinc uptake studies suggested that the zntA product was involved in the export of zinc ions out of cells. PMID:9696746

Morphological Control of Metal Oxide-Doped Zinc Oxide and Application to Cosmetics

NASA Astrophysics Data System (ADS)

Goto, Takehiro; Yin, Shu; Sato, Tsugio; Tanaka, Takumi

2012-06-01

Zinc oxide shows excellent transparency and ultraviolet radiation shielding ability, and is used for various cosmetics.1-3 However, it possesses high catalytic activity and lower dispersibility. Therefore, spherical particles of zinc oxide have been synthesized by soft solution reaction using zinc nitrate, ethylene glycol, sodium hydroxide and triethanolamine as starting materials. After dissolving these compounds in water, the solution was heated at 90°C for 1 h to form almost mono-dispersed spherical zinc oxide particles. The particle size changed depending on zinc ion concentration, ethylene glycol concentration and so on. Furthermore, with doping some metal ions, the phtocatalytic activity could be decreased. The obtained monodispersed metal ion-doped spherical zinc oxides showed excellent UV shielding ability and low photocatalytic activity. Therefore, they are expected to be used as cosmetics ingredients.

Effect of Magnesium Ion on the Zinc Electrodeposition from Acidic Sulfate Electrolyte

NASA Astrophysics Data System (ADS)

Tian, Lin; Xie, Gang; Yu, Xiao-Hua; Li, Rong-Xing; Zeng, Gui-Sheng

2012-02-01

The effects of Mg2+ ion on the zinc electrodeposition were systematically investigated in sulfuric acid solution through the characterizations of current efficiency (CE), power consumption (PC), deposit morphology, cathodic polarization, and cyclic voltammetry. The results demonstrate that there is no significant influence on CE and PC in the Mg2+ concentration range of 1 to 10 g L-1, but with a drastic decrease of the CE and rapid increase of PC at Mg2+ ion concentration above 15 g L-1. Based on the morphology observation and polarization curves, the presence of Mg2+ ions could also induce the coarse surface on the electrodeposited zinc accompanying the enhancement of the cathodic polarization, which becomes more distinct at a high concentration above 15 g L-1. Furthermore, hydrogen evolution could be promoted with the existence of Mg2+ ions according to cyclic voltammograms.

Acrosin activity in turkey spermatozoa: assay by clinical method and effect of zinc and benzamidine on the activity.

PubMed

Glogowski, J; Jankowski, J; Faruga, A; Ottobre, J S; Ciereszko, A

2001-09-15

We optimized a clinical assay developed for measuring total acrosin activity for mammalian and fish semen for use in turkey spermatozoa. The main modifications included dilution of semen to a final concentration of 25 to 1000 x 10(3) spermatozoa, an increase of Triton X-100 concentration to 0.05% and 1 hr preincubation without substrate, Acrosin activity in turkey spermatozoa was much higher than in human spermatozoa (about 100-times) but similar to that of boar sperm. To optimize this assay for turkey spermatozoa, it was necessary to use higher Triton X-100 concentrations in the reaction mixture. There was a better catalytic efficiency at higher temperatures and a special requirement for a preincubation period for proacrosin activation. We observed high inhibition of acrosin activity by zinc added during preincubation (90% at 0.01 mM of zinc chloride). Benzamidine also inhibited turkey acrosin, and the extent of inhibition was similar for the incubation or preincubation period. When zinc ions were added during incubation, this inhibition was lower (24%). The results suggest that zinc influences proacrosin activation of turkey spermatozoa. This influence may be important for successful long-term storage of spermatozoa in the hen's oviduct.

Effect of pulsed electric fields (PEF) on accumulation of selenium and zinc ions in Saccharomyces cerevisiae cells.

PubMed

Pankiewicz, Urszula; Sujka, Monika; Kowalski, Radosław; Mazurek, Artur; Włodarczyk-Stasiak, Marzena; Jamroz, Jerzy

2017-04-15

The cultures of Saccharomyces cerevisiae were treated with pulsed electric fields (PEF) in order to obtain a maximum accumulation of selenium and zinc ions (simultaneously) in the biomass. The following concentrations: 100μgSe/ml and 150μgZn/ml medium were assumed to be optimal for the maximum accumulation of these ions, that is 43.07mg/gd.m. for selenium and 14.48mg/gd.m. for zinc, in the cultures treated with PEF. At optimal PEF parameters: electric field strength of 3kV/cm and pulse width of 10μs after the treatment of 20-h culture for 10min, the maximum accumulation of both ions in the yeast cells was observed. Application of PEF caused the increase of ions accumulation by 65% for selenium and 100% for zinc. Optimization of PEF parameters led to the further rise in the both ions accumulation resulting in over 2-fold and 2.5-fold higher concentration of selenium and zinc. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suppressive effect of zinc ion on iNOS expression induced by interferon-gamma or tumor necrosis factor-alpha in murine keratinocytes.

PubMed

Yamaoka, J; Kume, T; Akaike, A; Miyachi, Y

2000-05-01

Zinc, an essential metal, is a critical component of zinc binding proteins such as zinc fingers, zinc enzymes and metallothioneins. Recently, evidence for its anti-inflammatory property in skin has been accumulating, as shown in the treatment of acne, alopecia and zinc deficiency. In cutaneous inflammations, a large amount of nitric oxide (NO) is produced through induction of inducible nitric oxide synthase (iNOS) under the influence of proinflammatory cytokines, resulting in tissue damages in skin, as clarified in other organs. Therefore, we asked if the effect of zinc on NO production and/or on iNOS expression in keratinocytes may explain the anti-inflammatory property of zinc in skin. Accordingly, we sought to determine in this study whether zinc ion may have effect on IFN-gamma or TNF-alpha induced NO production and iNOS expression in cultured murine keratinocytes. Ten microM of zinc ion remarkably suppressed cytokine-induced NO production in keratinocytes. Furthermore, zinc ion also suppressed cytokine-induced iNOS expression in the protein level as well as in the messenger RNA level. These results suggest the possibility that the suppressive effect of zinc ion on cytokine-induced NO production in keratinocytes may be in part implicated in the anti-inflammatory property of zinc in some of skin disorders.

Ion imprinted polymeric nanoparticles for selective separation and sensitive determination of zinc ions in different matrices

NASA Astrophysics Data System (ADS)

Shamsipur, Mojtaba; Rajabi, Hamid Reza; Pourmortazavi, Seied Mahdi; Roushani, Mahmoud

2014-01-01

Preparation of Zn2+ ion-imprinted polymer (Zn-IIP) nanoparticles is presented in this report. The Zn-IIP nanoparticles are prepared by dissolving stoichiometric amounts of zinc nitrate and selected chelating ligand, 3,5,7,20,40-pentahydroxyflavone, in 15 mL ethanol-acetonitrile (2:1; v/v) mixture as a porogen solvent in the presence of ethylene glycol-dimethacrylate (EGDMA) as cross-linking, methacrylic acid (MAA) as functional monomer, and 2,2-azobisisobutyronitrile (AIBN) as initiator. After polymerization, Cavities in the polymer particles corresponding to the Zn2+ ions were created by leaching the polymer in HCl aqueous solution. The synthesized IIPs were characterized by scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal analysis techniques. Also, the pH range for rebinding of Zn2+ ion on the IIP and equilibrium binding time were optimized, using flame atomic absorption spectrometry. In selectivity study, it was found that imprinting results increased affinity of the material toward Zn2+ ion over other competitor metal ions with the same charge and close ionic radius. The prepared IIPs were repeatedly used and regenerated for six times without any significant decrease in polymer binding affinities. Finally, the prepared sorbent was successfully applied to the selective recognition and determination of zinc ion in different real samples.

Notification: Evaluation of Cherryvale, Kansas National Zinc Company site

EPA Pesticide Factsheets

July 12, 2012. The purpose of this memorandum is to notify you that the OIG plans to conduct a review ofthe process followed by EPA Region 7 in the handling of site related contamination at the Cherryvale, Kansas National Zinc Company site.

Designing Hydrolytic Zinc Metalloenzymes

PubMed Central

2015-01-01

Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

Photochemically stable fluorescent heteroditopic ligands for zinc ion.

PubMed

Zhang, Lu; Zhu, Lei

2008-11-07

Photochemically stable fluorescent heteroditopic ligands (9 and 10) for zinc ion were prepared and studied. Two independent metal coordination-driven photophysical processes, chelation-enhanced fluorescence (CHEF) and internal (or intramolecular) charge transfer (ICT), were designed into our heteroditopic ligand framework. This strategy successfully relates three coordination states of a ligand, non-, mono-, and dicoordinated, to three fluorescence states, fluorescence OFF, ON at one wavelength, and ON at another wavelength. This ligand platform has provided chemical foundation for applications such as the quantification of zinc concentration over broad ranges (Zhang, L.; Clark, R. J.; Zhu, L. Chem.-Eur. J. 2008, 14, 2894-2903) and molecular logic functions (Zhang, L.; Whitfield, W. A.; Zhu, L. Chem. Commun. 2008, 1880-1882). The binding stoichiometries of dipicolylamino and 2,2'-bipyridyl, the two binding sites featured in heteroditopic ligands 7-10, were studied in acetonitrile using both Job's method of continuous variation and isothermal titration calorimetry (ITC). The fluorescence enhancement of 7-10 upon the formation of monozinc complexes (defined as the fluorescence quantum yield ratio of monozinc complex and free ligand) is qualitatively related to the highest occupied molecular orbital (HOMO) energy levels of their fluorophores. This is consistent with our hypothesis on the thermodynamics of the coordination-driven photophysical processes embodied in the designed heteroditopic system, which was supported by cyclic voltammetry studies. In conclusion, compounds 9 and 10 not only possess better photochemical stability but also display a higher degree of fluorescence turn-on upon formation of monozinc complexes than their vinyl counterparts 7 and 8.

Organic electrolyte-based rechargeable zinc-ion batteries using potassium nickel hexacyanoferrate as a cathode material

NASA Astrophysics Data System (ADS)

Chae, Munseok S.; Heo, Jongwook W.; Kwak, Hunho H.; Lee, Hochun; Hong, Seung-Tae

2017-01-01

This study demonstrates an organic electrolyte-based rechargeable zinc-ion battery (ZIB) using Prussian blue (PB) analogue potassium nickel hexacyanoferrate K0.86Ni[Fe(CN)6]0.954(H2O)0.766 (KNF-086) as the cathode material. KNF-086 is prepared via electrochemical extraction of potassium ions from K1.51Ni[Fe(CN)6]0.954(H2O)0.766 (KNF-151). The cell is composed of a KNF-086 cathode, a zinc metal anode, and a 0.5 M Zn(ClO4)2 acetonitrile electrolyte. This cell shows a reversible discharge capacity of 55.6 mAh g-1 at 0.2 C rate with the discharge voltage at 1.19 V (vs. Zn2+/Zn). As evidenced by Fourier electron density analysis with powder XRD data, the zinc-inserted phase is confirmed as Zn0.32K0.86Ni[Fe(CN)6]0.954(H2O)0.766 (ZKNF-086), and the position of the zinc ion in ZKNF-086 is revealed as the center of the large interstitial cavities of the cubic PB. Compared to KNF-086, ZKNF-086 exhibits a decreased unit cell parameter (0.9%) and volume (2.8%) while the interatomic distance of d(Fe-C) increased (from 1.84 to 1.98 Å), and the oxidation state of iron decreases from 3 to 2.23. The organic electrolyte system provides higher zinc cycling efficiency (>99.9%) than the aqueous system (ca. 80%). This result demonstrates an organic electrolyte-based ZIB, and offers a crucial basis for understanding the electrochemical intercalation chemistry of zinc ions in organic electrolytes.

Improved Electrochemical Detection of Zinc Ions Using Electrode Modified with Electrochemically Reduced Graphene Oxide

PubMed Central

Kudr, Jiri; Richtera, Lukas; Nejdl, Lukas; Xhaxhiu, Kledi; Vitek, Petr; Rutkay-Nedecky, Branislav; Hynek, David; Kopel, Pavel; Adam, Vojtech; Kizek, Rene

2016-01-01

Increasing urbanization and industrialization lead to the release of metals into the biosphere, which has become a serious issue for public health. In this paper, the direct electrochemical reduction of zinc ions is studied using electrochemically reduced graphene oxide (ERGO) modified glassy carbon electrode (GCE). The graphene oxide (GO) was fabricated using modified Hummers method and was electrochemically reduced on the surface of GCE by performing cyclic voltammograms from 0 to −1.5 V. The modification was optimized and properties of electrodes were determined using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The determination of Zn(II) was performed using differential pulse voltammetry technique, platinum wire as a counter electrode, and Ag/AgCl/3 M KCl reference electrode. Compared to the bare GCE the modified GCE/ERGO shows three times better electrocatalytic activity towards zinc ions, with an increase of reduction current along with a negative shift of reduction potential. Using GCE/ERGO detection limit 5 ng·mL−1 was obtained. PMID:28787832

Zinc at glutamatergic synapses.

PubMed

Paoletti, P; Vergnano, A M; Barbour, B; Casado, M

2009-01-12

It has long been known that the mammalian forebrain contains a subset of glutamatergic neurons that sequester zinc in their synaptic vesicles. This zinc may be released into the synaptic cleft upon neuronal activity. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and transporters. Among these targets, NMDA receptors appear particularly interesting because certain NMDA receptor subtypes (those containing the NR2A subunit) contain allosteric sites exquisitely sensitive to extracellular zinc. The existence of these high-affinity zinc binding sites raises the possibility that zinc may act both in a phasic and tonic mode. Changes in zinc concentration and subcellular zinc distribution have also been described in several pathological conditions linked to glutamatergic transmission dysfunctions. However, despite intense investigation, the functional significance of vesicular zinc remains largely a mystery. In this review, we present the anatomy and the physiology of the glutamatergic zinc-containing synapse. Particular emphasis is put on the molecular and cellular mechanisms underlying the putative roles of zinc as a messenger involved in excitatory synaptic transmission and plasticity. We also highlight the many controversial issues and unanswered questions. Finally, we present and compare two widely used zinc chelators, CaEDTA and tricine, and show why tricine should be preferred to CaEDTA when studying fast transient zinc elevations as may occur during synaptic activity.

Study of silicon doped with zinc ions and annealed in oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Privezentsev, V. V., E-mail: v.privezentsev@mail.ru; Kirilenko, E. P.; Goryachev, A. N.

2017-02-15

The results of studies of the surface layer of silicon and the formation of precipitates in Czochralski n-Si (100) samples implanted with {sup 64}Zn{sup +} ions with an energy of 50 keV and a dose of 5 × 10{sup 16} cm{sup –2} at room temperature and then oxidized at temperatures from 400 to 900°C are reported. The surface is visualized using an electron microscope, while visualization of the surface layer is conducted via profiling in depth by elemental mapping using Auger electron spectroscopy. The distribution of impurity ions in silicon is analyzed using a time-of-flight secondary-ion mass spectrometer. Using X-raymore » photoelectron spectroscopy, the chemical state of atoms of the silicon matrix and zinc and oxygen impurity atoms is studied, and the phase composition of the implanted and annealed samples is refined. After the implantation of zinc, two maxima of the zinc concentration, one at the wafer surface and the other at a depth of 70 nm, are observed. In this case, nanoparticles of the Zn metal phase and ZnO phase, about 10 nm in dimensions, are formed at the surface and in the surface layer. After annealing in oxygen, the ZnO · Zn{sub 2}SiO{sub 4} and Zn · ZnO phases are detected near the surface and at a depth of 50 nm, respectively.« less

HEPARIN-BINDING EGF CLEAVAGE MEDIATES ZINC-INDUCED EGF RECEPTOR PHOSPHORYLATION

EPA Science Inventory

We have previously shown that exposure to zinc ions can activate epidermal growth factor (EGF) receptor (EGFR) signaling in murine fibroblasts and A431 cells through a mechanism involving Src kinase. While studying the effects of zinc ions in normal human bronchial epithelial cel...

Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate

PubMed Central

Gao, Haixia; Boillat, Aurélien; Huang, Dongyang; Liang, Ce; Peers, Chris

2017-01-01

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP2). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP2. Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes. PMID:28716904

Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate.

PubMed

Gao, Haixia; Boillat, Aurélien; Huang, Dongyang; Liang, Ce; Peers, Chris; Gamper, Nikita

2017-08-01

M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP 2 ). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP 2 Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes.

Effect of pulse electric fields (PEF) on accumulation of magnesium and zinc ions in Saccharomyces cerevisiae cells.

PubMed

Pankiewicz, Urszula; Sujka, Monika; Włodarczyk-Stasiak, Marzena; Mazurek, Artur; Jamroz, Jerzy

2014-08-15

Cultures of Saccharomyces cerevisiae were treated with PEF to improve simultaneous accumulation of magnesium and zinc ions in the biomass. The results showed that the ions concentration in the medium and their mutual interactions affect accumulation in cells. Increasing the concentration of one ion in the medium reduced the accumulation of the second one, in the control as well as in the cells treated with PEF. Under optimized conditions, that is, on 15 min exposure of the 20 h grown culture to PEF of 5.0 kV/cm and 20 μs pulse width, accumulation of magnesium and zinc in yeast biomass reached maximum levels of 2.85 and 11.41 mg/gd.m., respectively, To summarize, optimization of ion pair concentration and PEF parameters caused a 1.5 or 2-fold increase of magnesium and zinc accumulation, respectively, in S. cerevisiae. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ion beam modification of zinc white pigment characterized by ex situ and in situ μ-Raman and XPS

NASA Astrophysics Data System (ADS)

Beck, L.; Gutiérrez, P. C.; Miro, S.; Miserque, F.

2017-10-01

Zinc oxide, known as zinc white, is one of the principal white pigments developed in the 18th century and was used by the Impressionist painters. ZnO as artists' pigment has occasionally been characterized by X-ray and ion beam techniques, but these studies are limited by the potential for visible radiation effect. Ion beam modifications of zinc oxide have extensively been investigated, but mainly for electronic and industrial applications. In this paper, we focus our investigation on ion beam modification of ZnO used as pigment. Two irradiation conditions have been used: an external 3 MeV proton micro-beam representative of PIXE analysis and 2 MeV H+ and 1.2 MeV Au + beams in vacuum to investigate irradiation modifications in electronic and nuclear energy loss regimes. Ion beam modification was characterized by ex situ and in situ micro-Raman spectrometry and XPS. The results shows that IBA of zinc white can be carried out safely in historical paintings with low current and dose.

Selective Solid-Phase Extraction of Zinc(II) from Environmental Water Samples Using Ion Imprinted Activated Carbon.

PubMed

Moniri, Elham; Panahi, Homayon Ahmad; Aghdam, Khaledeh; Sharif, Amir Abdollah Mehrdad

2015-01-01

A simple ion imprinted amino-functionalized sorbent was synthesized by coupling activated carbon with iminodiacetic acid, a functional compound for metal chelating, through cyanoric chloride spacer. The resulting sorbent has been characterized using FTIR spectroscopy, elemental analysis, and thermogravimetric analysis and evaluated for the preconcentration and determination of trace Zn(II) in environmental water samples. The optimum pH value for sorption of the metal ion was 6-7.5. The sorption capacity of the functionalized sorbent was 66.6 mg/g. The chelating sorbent can be reused for 10 cycles of sorption-desorption without any significant change in sorption capacity. A recovery of 100% was obtained for the metal ion with 0.5 M nitric acid as the eluent. Compared with nonimprinted polymer particles, the prepared Zn-imprinted sorbent showed high adsorption capacity, significant selectivity, and good site accessibility for Zn(II). Scatchard analysis revealed that the homogeneous binding sites were formed in the polymer. The equilibrium sorption data of Zn(II) by modified resin were analyzed by Langmuir, Freundlich, Temkin, and Redlich-Peterson models. Based on equilibrium adsorption data, the Langmuir, Freundlich, and Temkin constants were determined as 0.139, 12.82, and 2.34, respectively, at 25°C.

Incorporation of zinc into the coccoliths of the microalga Emiliania huxleyi.

PubMed

Santomauro, Giulia; Sun, Wei-Lin; Brümmer, Franz; Bill, Joachim

2016-04-01

The coccolithophore Emiliania huxleyi is covered with elaborated calcite plates, the so-called coccoliths, which are produced inside the cells. We investigated the incorporation of zinc into the coccoliths of E. huxleyi by applying different zinc and calcium amounts via the culture media and subsequently analyzing the zinc content in the cells and the Zn/Ca ratio of the coccoliths. To investigate the Zn/Ca ratio of coccoliths built in the manipulated media, the algae have first to be decalcified, i.e. coccolith free. We used a newly developed decalcification method to obtain 'naked' cells for cultivation. E. huxleyi proliferated and produced new coccoliths in all media with manipulated Zn/Ca ratios. The cells and the newly built coccoliths were investigated regarding their zinc content and their Zn/Ca ratio, respectively. High zinc amounts were taken up by the algae. The Zn/Ca ratio of the coccoliths was positively correlated to the Zn/Ca ratio of the applied media. The unique feature of the coccoliths was maintained also at high Zn/Ca ratios. We suggest the following pathway of the zinc ions into the coccoliths: first, the zinc ions are bound to the cell surface, followed by their transportation into the cytoplasm. Obviously, the zinc ions are removed afterwards into the coccolith vesicle, where the zinc is incorporated into the calcite coccoliths which are then extruded. The incorporation of toxic zinc ions into the coccoliths possibly due to a new function of the coccoliths as detoxification sites is discussed.

Eluted zinc ions stimulate osteoblast differentiation and mineralization in human dental pulp stem cells for bone tissue engineering.

PubMed

Yusa, Kazuyuki; Yamamoto, Osamu; Iino, Mitsuyoshi; Takano, Hiroshi; Fukuda, Masayuki; Qiao, Zhiwei; Sugiyama, Toshihiro

2016-11-01

Zinc is an essential element for proliferation, differentiation and survival in various cell types. In a previous study, we found that zinc ions released from zinc-modified titanium surfaces (eluted zinc ions; EZ) stimulate cell viability, osteoblast marker gene expression and calcium deposition in human bone marrow-derived mesenchymal cells (hBMCs). The aim of the present study was to investigate the effects of EZ on osteoblast differentiation among dental pulp stem cells (DPSCs) in vitro. In this study, we evaluated the effects of EZ on osteogenesis in DPSCs. Osteoblast and osteoclast marker gene expression was evaluated by real-time PCR. We also evaluated alkaline phosphatase (ALP) staining and calcium deposition. We found that EZ stimulated osteoblast marker gene (type I collagen, alkaline phosphatase (ALP), osteocalcin (OCN) and Runx2) expression, vascular endothelial growth factor A (VEGF-A), and TGF-beta signaling pathway-related gene expression after 7days of incubation. Osteoclastogenesis occurs in a receptor for activated nuclear-factor kappa B ligand (RANKL)/osteoprotegerin (OPG)-independent manner. Real-time PCR analysis revealed that EZ did not affect RANKL or OPG mRNA expression. It was also revealed that EZ induced alkaline phosphatase (ALP) staining and calcium deposition in DPSCs. Collectively, these results demonstrate the potential for clinical application to prospective treatment of bone diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preferential uptake of ammonium ions by zinc ferrocyanide

NASA Technical Reports Server (NTRS)

Braterman, P. S.; Arrhenius, G.; Hui, S.; Paplawsky, W.; Miller, S. L. (Principal Investigator)

1995-01-01

The concentration of ammonia from dilute aqueous solution could have facilitated many prebiotic reactions. This may be especially true if this concentration involves incorporation into an organized medium. We have shown that (unlike iron(III) ferrocyanide) zinc ferrocyanide,Zn2Fe(CN)6 xH2O, preferentially takes up ammonium ions from 0.01 M NH4Cl to give the known material Zn3(NH4)2[Fe(CN)6]2 xH2O, even in the presence of 0.01 M KCl. KCl alone gave Zn3K2[Fe(CN)6]2 xH2O. Products were characterized by elemental (CHN) analysis and powder X-ray diffraction (XRD). We attribute the remarkable specificity for the ammonium ion to the open framework of the product, which offers enough space for hydrogen-bonded ammonium ions, and infer that other inorganic materials with internal spaces rich in water may show a similar preference.

Rechargeable nickel-3D zinc batteries: An energy-dense, safer alternative to lithium-ion.

PubMed

Parker, Joseph F; Chervin, Christopher N; Pala, Irina R; Machler, Meinrad; Burz, Michael F; Long, Jeffrey W; Rolison, Debra R

2017-04-28

The next generation of high-performance batteries should include alternative chemistries that are inherently safer to operate than nonaqueous lithium-based batteries. Aqueous zinc-based batteries can answer that challenge because monolithic zinc sponge anodes can be cycled in nickel-zinc alkaline cells hundreds to thousands of times without undergoing passivation or macroscale dendrite formation. We demonstrate that the three-dimensional (3D) zinc form-factor elevates the performance of nickel-zinc alkaline cells in three fields of use: (i) >90% theoretical depth of discharge (DOD Zn ) in primary (single-use) cells, (ii) >100 high-rate cycles at 40% DOD Zn at lithium-ion-commensurate specific energy, and (iii) the tens of thousands of power-demanding duty cycles required for start-stop microhybrid vehicles. Copyright © 2017, American Association for the Advancement of Science.

Modulation of neuronal signal transduction and memory formation by synaptic zinc.

PubMed

Sindreu, Carlos; Storm, Daniel R

2011-01-01

The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over 50 years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock-out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling.

Modulation of Neuronal Signal Transduction and Memory Formation by Synaptic Zinc

PubMed Central

Sindreu, Carlos; Storm, Daniel R.

2011-01-01

The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over 50 years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock-out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling. PMID:22084630

A Photoluminescence Study of the Changes Induced in the Zinc White Pigment by Formation of Zinc Complexes

PubMed Central

Artesani, Alessia; Gherardi, Francesca; Nevin, Austin; Valentini, Gianluca; Comelli, Daniela

2017-01-01

It is known that oil paintings containing zinc white are subject to rapid degradation. This is caused by the interaction between the active groups of binder and the metal ions of the pigment, which gives rise to the formation of new zinc complexes (metal soaps). Ongoing studies on zinc white paints have been limited to the chemical mechanisms that lead to the formation of zinc complexes. On the contrary, little is known of the photo-physical changes induced in the zinc oxide crystal structure following this interaction. Time-resolved photoluminescence spectroscopy has been applied to follow modifications in the luminescent zinc white pigment when mixed with binder. Significant changes in trap state photoluminescence emissions have been detected: the enhancement of a blue emission combined with a change of the decay kinetic of the well-known green emission. Complementary data from molecular analysis of paints using Fourier transform infrared spectroscopy confirms the formation of zinc carboxylates and corroborates the mechanism for zinc complexes formation. We support the hypothesis that zinc ions migrate into binder creating novel vacancies, affecting the photoluminescence intensity and lifetime properties of zinc oxide. Here, we further demonstrate the advantages of a time-resolved photoluminescence approach for studying defects in semiconductor pigments. PMID:28772700

Zinc-mediated Allosteric Inhibition of Caspase-6*

PubMed Central

Velázquez-Delgado, Elih M.; Hardy, Jeanne A.

2012-01-01

Zinc and caspase-6 have independently been implicated in several neurodegenerative disorders. Depletion of zinc intracellularly leads to apoptosis by an unknown mechanism. Zinc inhibits cysteine proteases, including the apoptotic caspases, leading to the hypothesis that zinc-mediated inhibition of caspase-6 might contribute to its regulation in a neurodegenerative context. Using inductively coupled plasma optical emission spectroscopy, we observed that caspase-6 binds one zinc per monomer, under the same conditions where the zinc leads to complete loss of enzymatic activity. To understand the molecular details of zinc binding and inhibition, we performed an anomalous diffraction experiment above the zinc edge. The anomalous difference maps showed strong 5σ peaks, indicating the presence of one zinc/monomer bound at an exosite distal from the active site. Zinc was not observed bound to the active site. The zinc in the exosite was liganded by Lys-36, Glu-244, and His-287 with a water molecule serving as the fourth ligand, forming a distorted tetrahedral ligation sphere. This exosite appears to be unique to caspase-6, as the residues involved in zinc binding were not conserved across the caspase family. Our data suggest that binding of zinc at the exosite is the primary route of inhibition, potentially locking caspase-6 into the inactive helical conformation. PMID:22891250

Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc.

PubMed

Cao, Kun; Li, Nan; Wang, Hongcui; Cao, Xin; He, Jiaojiao; Zhang, Bing; He, Qing-Yu; Zhang, Gong; Sun, Xuesong

2018-04-20

Zinc is an essential metal in bacteria. One important bacterial zinc transporter is AdcA, and most bacteria possess AdcA homologs that are single-domain small proteins due to better efficiency of protein biogenesis. However, a double-domain AdcA with two zinc-binding sites is significantly overrepresented in Streptococcus species, many of which are major human pathogens. Using molecular simulation and experimental validations of AdcA from Streptococcus pyogenes , we found here that the two AdcA domains sequentially stabilize the structure upon zinc binding, indicating an organization required for both increased zinc affinity and transfer speed. This structural organization appears to endow Streptococcus species with distinct advantages in zinc-depleted environments, which would not be achieved by each single AdcA domain alone. This enhanced zinc transport mechanism sheds light on the significance of the evolution of the AdcA domain fusion, provides new insights into double-domain transporter proteins with two binding sites for the same ion, and indicates a potential target of antimicrobial drugs against pathogenic Streptococcus species. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Adsorption of metal ions by pecan shell-based granular activated carbons.

PubMed

Bansode, R R; Losso, J N; Marshall, W E; Rao, R M; Portier, R J

2003-09-01

The present investigation was undertaken to evaluate the adsorption effectiveness of pecan shell-based granular activated carbons (GACs) in removing metal ions (Cu(2+), Pb(2+), Zn(2+)) commonly found in municipal and industrial wastewater. Pecan shells were activated by phosphoric acid, steam or carbon dioxide activation methods. Metal ion adsorption of shell-based GACs was compared to the metal ion adsorption of a commercial carbon, namely, Calgon's Filtrasorb 200. Adsorption experiments were conducted using solutions containing all three metal ions in order to investigate the competitive effects of the metal ions as would occur in contaminated wastewater. The results obtained from this study showed that acid-activated pecan shell carbon adsorbed more lead ion and zinc ion than any of the other carbons, especially at carbon doses of 0.2-1.0%. However, steam-activated pecan shell carbon adsorbed more copper ion than the other carbons, particularly using carbon doses above 0.2%. In general, Filtrasorb 200 and carbon dioxide-activated pecan shell carbons were poor metal ion adsorbents. The results indicate that acid- and steam-activated pecan shell-based GACs are effective metal ion adsorbents and can potentially replace typical coal-based GACs in treatment of metal contaminated wastewater.

Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.

PubMed

Bottomley, Matthew J; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-09-26

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR.HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions.

Promotive Effect of Zinc Ions on the Vitality, Migration, and Osteogenic Differentiation of Human Dental Pulp Cells.

PubMed

An, Shaofeng; Gong, Qimei; Huang, Yihua

2017-01-01

Zinc is an essential trace element for proper cellular function and bone formation. However, its exact role in the osteogenic differentiation of human dental pulp cells (hDPCs) has not been fully clarified before. Here, we speculated that zinc may be effective to regulate their growth and osteogenic differentiation properties. To test this hypothesis, different concentrations (1 × 10 -5 , 4 × 10 -5 , and 8 × 10 -5  M) of zinc ions (Zn 2+ ) were added to the basic growth culture medium and osteogenic inductive medium. Cell viability and migration were measured by cell counting kit-8 (CCK-8) and transwell migration assay in the basic growth culture medium, respectively. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expression levels of selective osteogenic differentiation markers and zinc transporters. Alkaline phosphatase (ALP) activity analysis and alizarin red S staining were used to investigate the mineralization of hDPCs. Exposure of hDPCs to Zn 2+ stimulated their viability and migration capacity in a dose- and time-dependent manner. RT-qPCR assay revealed elevated expression levels of osteogenic differentiation-related genes and zinc transporters genes in various degrees. ALP activity was also increased with elevated Zn 2+ concentrations and extended culture periods, but enhanced matrix nodules formation were observed only in 4 × 10 -5 and 8 × 10 -5  M Zn 2+ groups. These findings suggest that specific concentrations of Zn 2+ could potentiate the vitality, migration, and osteogenic differentiation of hDPCs. We may combine optimum zinc element into pulp capping materials to improve their biological performance.

Assignment of the zinc ligands in RsrA, a redox-sensing ZAS protein from Streptomyces coelicolor.

PubMed

Zdanowski, Konrad; Doughty, Phillip; Jakimowicz, Piotr; O'Hara, Liisa; Buttner, Mark J; Paget, Mark S B; Kleanthous, Colin

2006-07-11

ZAS proteins are widespread bacterial zinc-containing anti-sigma factors that regulate the activity of sigma factors in response to diverse cues. One of the best characterized ZAS proteins is RsrA from Streptomyces coelicolor, which responds to disulfide stress. Zn-RsrA binds and represses the transcriptional activity of sigmaR in the reducing environment of the cytoplasm but undergoes reversible, intramolecular disulfide bond formation during oxidative stress. This expels the single metal ion and causes dramatic structural changes in RsrA that result in its dissociation from sigmaR, leaving the sigma factor free to activate the transcription of antioxidant genes. We showed recently that Zn2+ serves a critical role in modulating the redox activity of RsrA thiols but uncertainty remains as to how the metal ion is coordinated in RsrA and related ZAS proteins. Using a combination of random and site-specific mutagenesis with zinc K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy, we have assigned unambiguously the metal ligands in RsrA, thereby distinguishing between the different ligation models that have been proposed. The data show that the zinc site in RsrA is comprised of Cys11, His37, Cys41, and Cys44. Three of these residues are part of a conserved ZAS-specific sequence motif (H37xxxC41xxC44), with the fourth ligand, Cys11, found in a subset of ZAS proteins. Cys11 and Cys44 form the trigger disulfide in RsrA, explaining why the metal ion is expelled during oxidation. We discuss these data in the context of redox sensing by RsrA and the sensory mechanisms of other ZAS proteins.

Conformational Analysis on structural perturbations of the zinc finger NEMO

NASA Astrophysics Data System (ADS)

Godwin, Ryan; Salsbury, Freddie; Salsbury Group Team

2014-03-01

The NEMO (NF-kB Essential Modulator) Zinc Finger protein (2jvx) is a functional Ubiquitin-binding domain, and plays a role in signaling pathways for immune/inflammatory responses, apoptosis, and oncogenesis [Cordier et al., 2008]. Characterized by 3 cysteines and 1 histidine residue at the active site, the biologically occurring, bound zinc configuration is a stable structural motif. Perturbations of the zinc binding residues suggest conformational changes in the 423-atom protein characterized via analysis of all-atom molecular dynamics simulations. Structural perturbations include simulations with and without a zinc ion and with and without de-protonated cysteines, resulting in four distinct configurations. Simulations of various time scales show consistent results, yet the longest, GPU driven, microsecond runs show more drastic structural and dynamic fluctuations when compared to shorter duration time-scales. The last cysteine residue (26 of 28) and the helix on which it resides exhibit a secondary, locally unfolded conformation in addition to its normal bound conformation. Combined analytics elucidate how the presence of zinc and/or protonated cysteines impact the dynamics and energetic fluctuations of NEMO. Comprehensive Cancer Center of Wake Forest University Computational Biosciences shared resource supported by NCI CCSG P30CA012197.

Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-binding Domain*S⃞

PubMed Central

Bottomley, Matthew J.; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-01-01

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR·HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions. PMID:18614528

Removal of toxic zinc from water/wastewater using eucalyptus seeds activated carbon: non-linear regression analysis.

PubMed

Senthil Kumar, Ponnusamy; Saravanan, Anbalagan; Anish Kumar, Kodyingil; Yashwanth, Ramesh; Visvesh, Sridharan

2016-08-01

In the present study, a novel activated carbon was prepared from low-cost eucalyptus seeds, which was utilised for the effectively removal of toxic zinc from the water/wastewater. The prepared adsorbent was studied by Fourier transform infrared spectroscopy and scanning electron microscopic characterisation studies. Adsorption process was experimentally performed for optimising the influencing factors such as adsorbent dosage, solution pH, contact time, initial zinc concentration, and temperature for the maximum removal of zinc from aqueous solution. Adsorption isotherm of zinc removal was ensued Freundlich model, and the kinetic model ensued pseudo-second order model. Langmuir monolayer adsorption capacity of the adsorbent for zinc removal was evaluated as 80.37 mg/g. The results of the thermodynamic studies suggested that the adsorption process was exothermic, thermodynamically feasible and impulsive process. Finally, a batch adsorber was planned to remove zinc from known volume and known concentration of wastewater using best obeyed model such as Freundlich. The experimental details showed the newly prepared material can be effectively utilised as a cheap material for the adsorption of toxic metal ions from the contaminated water.

Zinc-Permeable Ion Channels: Effects on Intracellular Zinc Dynamics and Potential Physiological/Pathophysiological Significance

PubMed Central

Inoue, Koichi; O'Bryant, Zaven; Xiong, Zhi-Gang

2015-01-01

Zinc (Zn2+) is one of the most important trace metals in the body. It is necessary for the normal function of a large number of proteins including enzymes and transcription factors. While extracellular fluid may contain up to micromolar Zn2+, intracellular Zn2+ concentration is generally maintained at a subnanomolar level; this steep gradient across the cell membrane is primarily attributable to Zn2+ extrusion by Zn2+ transporting systems. Interestingly, systematic investigation has revealed that activities, previously believed to be dependent on calcium (Ca2+), may be partially mediated by Zn2+. This is also supported by new findings that some Ca2+-permeable channels such as voltage-dependent calcium channels (VDCCs), N-methyl-D-aspartate receptors (NMDA), and amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPA-Rs) are also permeable to Zn2+. Thus, the importance of Zn2+ in physiological and pathophysiological processes is now more widely appreciated. In this review, we describe Zn2+-permeable membrane molecules, especially Zn2+-permeable ion channels, in intracellular Zn2+dynamics and Zn2+ mediated physiology/pathophysiology. PMID:25666796

Structure-property-composition relationships in doped zinc oxides: enhanced photocatalytic activity with rare earth dopants.

PubMed

Goodall, Josephine B M; Illsley, Derek; Lines, Robert; Makwana, Neel M; Darr, Jawwad A

2015-02-09

In this paper, we demonstrate the use of continuous hydrothermal flow synthesis (CHFS) technology to rapidly produce a library of 56 crystalline (doped) zinc oxide nanopowders and two undoped samples, each with different particle properties. Each sample was produced in series from the mixing of an aqueous stream of basic zinc nitrate (and dopant ion or modifier) solution with a flow of superheated water (at 450 °C and 24.1 MPa), whereupon a crystalline nanoparticle slurry was rapidly formed. Each composition was collected in series, cleaned, freeze-dried, and then characterized using analytical methods, including powder X-ray diffraction, transmission electron microscopy, Brunauer-Emmett-Teller surface area measurement, X-ray photoelectron spectroscopy, and UV-vis spectrophotometry. Photocatalytic activity of the samples toward the decolorization of methylene blue dye was assessed, and the results revealed that transition metal dopants tended to reduce the photoactivity while rare earth ions, in general, increased the photocatalytic activity. In general, low dopant concentrations were more beneficial to having greater photodecolorization in all cases.

Revisiting the open-framework zinc hexacyanoferrate: The role of ternary electrolyte and sodium-ion intercalation mechanism

NASA Astrophysics Data System (ADS)

Niu, Lei; Chen, Liang; Zhang, Jun; Jiang, Ping; Liu, Zhaoping

2018-03-01

Non-flammable rechargeable aqueous sodium-ion batteries (RASB) made from natural abundant resources offer promising opportunities in large-scale energy storage, yet the low energy density as well as low voltage output and the limited cycle life hinder their practical applications. Here, we develop a high-voltage RASB based on rhombohedral zinc hexacyanoferrate as cathode materials, carbon-coated NaTi2(PO4)3 as anode materials and ternary NaClO4-H2O-polyethylene glycol (Na-H2O-PEG) as electrolyte to overcome these drawbacks. Such an RASB can deliver a high voltage output of 1.6 V with a specific energy density of 59 Wh kg-1 based on the total mass of active electrode materials. In addition, it possesses an excellent rate capability as an ultra-capacitor (2.7 kW kg-1). The capacity retention more than 91% is obtained after 100 cycles. Finally, a reversible phase transformation between rhombohedral Zn3[Fe(CN)6]2 and rhombohedral Na2Zn3[Fe(CN)6]2 that are accompanied by the insertion/extraction of sodium ion in zinc hexacyanoferrate is unveiled.

CaSO4 Scale Inhibition by a Trace Amount of Zinc Ion in Piping System

NASA Astrophysics Data System (ADS)

Mangestiyono, W.; Sutrisno

2017-05-01

Usually, a small steam generator is not complemented by equipment such as demineralization and chlorination process apparatus since the economic aspect was a precedence. Such phenomenon was uncovered in a case study of green tea industrial process in which the boiler capacity was not more than 1 ton/hour. The operation of the small boiler affected the scaling process in its piping system. In a year operation, there was already a large scale of calcium attached to the inner surface of the pipe. Such large scale formed a layer and decreased the overall heat transfer coefficient, prolonged the process time and decreased the production. The aim of the current research was to solve the problem through a laboratory research to inhibit the CaSO4 scale formation by the addition of trace amounts of zinc ion. This research was conducted through a built in-house experimental rig which consisted of a dosing pump for controlling the flow rate and a thermocouple to control the temperature. Synthesis solution was prepared with 3,500 ppm concentration of CaCl2 and Na2SO4. The concentration of zinc was set at 0.00; 5.00 and 10.00 ppm. The data found were characterized by scanning electron microscopy (SEM) to analyze crystal polymorph as the influence of zinc ion addition. The induction time was also investigated to analyze the nucleation time, and it was found on the 9th, 13th, and 19th minute of the zinc ion addition of 0.00, 5.00 and 10.00 ppm. After running for a four-hour duration, the scale grow-rate was found to be 5.799; 5.501 and 4.950 × 10-3 gr/min for 0.00; 5.00 and 10.00 ppm of zinc addition at 50 °C.

Toward rules relating zinc finger protein sequences and DNA binding site preferences.

PubMed

Desjarlais, J R; Berg, J M

1992-08-15

Zinc finger proteins of the Cys2-His2 type consist of tandem arrays of domains, where each domain appears to contact three adjacent base pairs of DNA through three key residues. We have designed and prepared a series of variants of the central zinc finger within the DNA binding domain of Sp1 by using information from an analysis of a large data base of zinc finger protein sequences. Through systematic variations at two of the three contact positions (underlined), relatively specific recognition of sequences of the form 5'-GGGGN(G or T)GGG-3' has been achieved. These results provide the basis for rules that may develop into a code that will allow the design of zinc finger proteins with preselected DNA site specificity.

An X-ray absorption spectroscopy study of the inversion degree in zinc ferrite nanocrystals dispersed on a highly porous silica aerogel matrix.

PubMed

Carta, D; Marras, C; Loche, D; Mountjoy, G; Ahmed, S I; Corrias, A

2013-02-07

The structural properties of zinc ferrite nanoparticles with spinel structure dispersed in a highly porous SiO(2) aerogel matrix were compared with a bulk zinc ferrite sample. In particular, the details of the cation distribution between the octahedral (B) and tetrahedral (A) sites of the spinel structure were determined using X-ray absorption spectroscopy. The analysis of both the X-ray absorption near edge structure and the extended X-ray absorption fine structure indicates that the degree of inversion of the zinc ferrite spinel structures varies with particle size. In particular, in the bulk microcrystalline sample, Zn(2+) ions are at the tetrahedral sites and trivalent Fe(3+) ions occupy octahedral sites (normal spinel). When particle size decreases, Zn(2+) ions are transferred to octahedral sites and the degree of inversion is found to increase as the nanoparticle size decreases. This is the first time that a variation of the degree of inversion with particle size is observed in ferrite nanoparticles grown within an aerogel matrix.

Crystallographic snapshots of active site metal shift in E. coli fructose 1,6-bisphosphate aldolase.

PubMed

Tran, Huyen-Thi; Lee, Seon-Hwa; Ho, Thien-Hoang; Hong, Seung-Hye; Huynh, Kim-Hung; Ahn, Yeh-Jin; Oh, Deok-Kun; Kang, Lin-Woo

2016-12-01

Fructose 1,6-bisphosphate aldolase (FBA) is important for both glycolysis and gluconeogenesis in life. Class II (zinc dependent) FBA is an attractive target for the development of antibiotics against protozoa, bacteria, and fungi, and is also widely used to produce various high-value stereoisomers in the chemical and pharmaceutical industry. In this study, the crystal structures of class II Escherichia coli FBA (EcFBA) were determined from four different crystals, with resolutions between 1.8 Å and 2.0 Å. Native EcFBA structures showed two separate sites of Zn1 (interior position) and Zn2 (active site surface position) for Zn2＋ ion. Citrate and TRIS bound EcFBA structures showed Zn2＋ position exclusively at Zn2. Crystallographic snapshots of EcFBA structures with and without ligand binding proposed the rationale of metal shift at the active site, which might be a hidden mechanism to keep the trace metal cofactor Zn2＋ within EcFBA without losing it. [BMB Reports 2016; 49(12): 681-686].

78 FR 46948 - Proposed Agreement Regarding Site Costs and Covenants Not To Sue for American Lead and Zinc Mill...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... Not To Sue for American Lead and Zinc Mill Site, Ouray County, Colorado AGENCY: Environmental... provides for Settling Party's payment of certain response costs incurred at the American Lead and Zinc Mill... reference the American Lead and Zinc Mill Site, the EPA Docket No. CERCLA-08-2013- 0004. The Agency's...

Serum alkaline phosphatase activity during zinc deficiency and long-term inflammatory stress.

PubMed

Naber, T H; Baadenhuysen, H; Jansen, J B; van den Hamer, C J; van den Broek, W

1996-05-30

A decrease in serum zinc can be caused by a real zinc deficiency but can also be caused by an apparent zinc deficiency, e.g. in inflammatory stress. The aim of this study was to evaluate the diagnostic power of serum alkaline phosphatase (AP) activity in the discrimination between pathophysiologic states of "real" and "apparent" zinc deficiency. A decrease in serum zinc was induced in growing and adult rats, by providing a diet low in zinc and by causing inflammatory stress. AP activity was determined using reagents low or enriched in zinc. Serum AP was decreased in zinc-deficient adult rats (P < 0.01). In zinc-deficient growing rats AP activity was not different from normal rats but AP activity decreased rapidly. In the same growing rats a significant difference was found in AP activities determined using buffers low and enriched in zinc (P < 0.001) between both groups of rats. After inducing inflammatory stress a decrease in AP activity (P < 0.01) and serum zinc (P < 0.001) was seen during the first few days. After the initial phase of inflammation AP activity normalized, serum zinc showed a rise which after correction for the decrease in serum albumin reached the level of the control rats. A difference in AP activity in buffers low and enriched in zinc was observed only during the first few days after induction of inflammatory stress (P < 0.001). Probably the method of measurement of the difference in enzyme activity, using buffers low and enriched in zinc, can be used as an indication for zinc deficiency in situations with changing AP enzyme concentrations. AP activity is decreased during the initial phase of inflammatory stress due to a decrease in serum zinc.

Two Active Site Divalent Ions in the Crystal Structure of the Hammerhead Ribozyme Bound to a Transition State Analogue.

PubMed

Mir, Aamir; Golden, Barbara L

2016-02-02

The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. On the basis of this crystal structure as well as a wealth of biochemical studies, we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.

An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

PubMed Central

Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.

2016-01-01

The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

Influence of extracellular zinc on M1 microglial activation.

PubMed

Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

2017-02-27

Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl 2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia-reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.

Influence of extracellular zinc on M1 microglial activation

PubMed Central

Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

2017-01-01

Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30–60 μM ZnCl2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia–reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory. PMID:28240322

LiZIP3 is a cellular zinc transporter that mediates the tightly regulated import of zinc in Leishmania infantum parasites

PubMed Central

Carvalho, Sandra; da Silva, Rosa Barreira; Shawki, Ali; Castro, Helena; Lamy, Márcia; Eide, David; Costa, Vítor; Mackenzie, Bryan; Tomás, Ana M.

2016-01-01

Summary Cellular zinc homeostasis ensures that the intracellular concentration of this element is kept within limits that enable its participation in critical physiological processes without exerting toxic effects. We report here the identification and characterization of the first mediator of zinc homeostasis in Leishmania infantum, LiZIP3, a member of the ZIP family of divalent metal-ion transporters. The zinc transporter activity of LiZIP3 was first disclosed by its capacity to rescue the growth of Saccharomyces cerevisiae strains deficient in zinc acquisition. Subsequent expression of LiZIP3 in Xenopus laevis oocytes was shown to stimulate the uptake of a broad range of metal ions, among which Zn2+ was the preferred LiZIP3 substrate (K0.5 ≈ 0.1 μM). Evidence that LiZIP3 functions as a zinc importer in L. infantum came from the observations that the protein locates to the cell membrane and that its overexpression leads to augmented zinc internalization. Importantly, expression and cell-surface location of LiZIP3 are lost when parasites face high zinc bioavailability. LiZIP3 decline in response to zinc is regulated at the mRNA level in a process involving (a) short-lived protein(s). Collectively, our data reveal that LiZIP3 enables L. infantum to acquire zinc in a highly regulated manner, hence contributing to zinc homeostasis. PMID:25644708

Active-site solvent replenishment observed during human carbonic anhydrase II catalysis.

PubMed

Kim, Jin Kyun; Lomelino, Carrie L; Avvaru, Balendu Sankara; Mahon, Brian P; McKenna, Robert; Park, SangYoun; Kim, Chae Un

2018-01-01

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO 2 /HCO 3 - . Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO 2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (W I ') is observed next to the previously observed intermediate water W I , and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH - on CO 2 . This mechanism explains how the zinc-bound water (W Zn ) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first 'physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

Enhanced antibacterial activity of zinc oxide nanoparticles synthesized using Petroselinum crispum extracts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stan, Manuela, E-mail: manuela.stan@itim-cj.ro; Popa, Adriana; Toloman, Dana

The present contribution reports the synthesis of zinc oxide nanoparticles (ZnO NPs) using aqueous leaf and root extracts of Petroselinum crispum (parsley) and characterization of as-prepared samples. ZnO NPs are subjected to X-ray diffraction (XRD), transmission electron microscopy (TEM) and electron paramagnetic resonance (EPR) studies. The XRD studies reveal a hexagonal wurtzite structure without supplementary diffraction lines for all ZnO samples. TEM analysis shows that the particle size is influenced by the type of plant extract. The EPR spectra indicate the presence of Mn{sup 2+} ions in ZnO sample synthesized using P. crispum leaf extract, while zinc vacancy complexes andmore » oxygen vacancies are evidenced in all analyzed samples. ZnO NPs synthesized using P. crispum extracts exhibit increased (2-16 times) antibacterial activity as compared to chemically synthesized ZnO NPs.« less

Enhanced antibacterial activity of zinc oxide nanoparticles synthesized using Petroselinum crispum extracts

NASA Astrophysics Data System (ADS)

Stan, Manuela; Popa, Adriana; Toloman, Dana; Silipas, Teofil-Danut; Vodnar, Dan Cristian; Katona, Gabriel

2015-12-01

The present contribution reports the synthesis of zinc oxide nanoparticles (ZnO NPs) using aqueous leaf and root extracts of Petroselinum crispum (parsley) and characterization of as-prepared samples. ZnO NPs are subjected to X-ray diffraction (XRD), transmission electron microscopy (TEM) and electron paramagnetic resonance (EPR) studies. The XRD studies reveal a hexagonal wurtzite structure without supplementary diffraction lines for all ZnO samples. TEM analysis shows that the particle size is influenced by the type of plant extract. The EPR spectra indicate the presence of Mn2+ ions in ZnO sample synthesized using P. crispum leaf extract, while zinc vacancy complexes and oxygen vacancies are evidenced in all analyzed samples. ZnO NPs synthesized using P. crispum extracts exhibit increased (2-16 times) antibacterial activity as compared to chemically synthesized ZnO NPs.

Crystal structure of E. coli ZinT with one zinc-binding mode and complexed with citrate.

PubMed

Chen, Jinli; Wang, Lulu; Shang, Fei; Dong, Yuesheng; Ha, Nam-Chul; Nam, Ki Hyun; Quan, Chunshan; Xu, Yongbin

2018-06-02

The ZnuABC ATP-binding cassette transporter found in gram-negative bacteria has been implicated in ensuring adequate zinc import into Zn(II)-poor environments. ZinT is an essential component of ZnuABC and contributes to metal transport by transferring metals to ZnuA, which delivers them to ZnuB in periplasmic zinc recruitment. Although several structures of E. coli ZinT have been reported, its zinc-binding sites and oligomeric state have not been clearly identified. Here, we report the crystal structure of E. coli ZinT at 1.76 Å resolution. This structure contains one zinc ion in its calycin-like domain, and this ion is coordinated by three highly conserved histidine residues (His167, His176 and His178). Moreover, three oxygen atoms (O 1 , O 6 and O 7 ) from the citrate molecule interact with zinc, giving the zinc ion stable octahedral coordination. Our EcZinT structure shows the fewest zinc ions bound of all reported EcZinT structures. Crystallographic packing and size exclusion chromatography suggest that EcZinT prefers to form monomers in solution. Our results provide insights into the molecular function of ZinT. Copyright © 2018. Published by Elsevier Inc.

Chemical stability and electrical performance of dual-active-layered zinc-tin-oxide/indium-gallium-zinc-oxide thin-film transistors using a solution process.

PubMed

Kim, Chul Ho; Rim, You Seung; Kim, Hyun Jae

2013-07-10

We investigated the chemical stability and electrical properties of dual-active-layered zinc-tin-oxide (ZTO)/indium-gallium-zinc-oxide (IGZO) structures (DALZI) with the durability of the chemical damage. The IGZO film was easily corroded or removed by an etchant, but the DALZI film was effectively protected by the high chemical stability of ZTO. Furthermore, the electrical performance of the DALZI thin-film transistor (TFT) was improved by densification compared to the IGZO TFT owing to the passivation of the pin holes or pore sites and the increase in the carrier concentration due to the effect of Sn(4+) doping.

Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mir, Aamir; Golden, Barbara L.

2015-11-09

The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the p K A of G12. Finally, on the basis ofmore » this crystal structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.« less

Spectroscopic investigation of zinc tellurite glasses doped with Yb3 + and Er3 + ions

NASA Astrophysics Data System (ADS)

Bilir, Gökhan; Kaya, Ayfer; Cinkaya, Hatun; Eryürek, Gönül

2016-08-01

This paper presents a detailed spectroscopic investigation of zinc tellurite glasses with the compositions (0.80 - x - y) TeO2 + (0.20) ZnO + xEr2O3 + yYb2O3 (x = 0, y = 0; x = 0.004, y = 0; x = 0, y = 0.05 and x = 0.004, y = 0.05 per moles). The samples were synthesized by the conventional melt quenching method. The optical absorption and emission measurements were conducted at room temperature to determine the spectral properties of lanthanides doped zinc tellurite glasses and, to study the energy transfer processes between dopant lanthanide ions. The band gap energies for both direct and indirect possible transitions and the Urbach energies were measured from the absorption spectra. The absorption spectra of the samples were analyzed by using the Judd-Ofelt approach. The effect of the ytterbium ions on the emission properties of erbium ions was investigated and the energy transfer processes between dopant ions were studied by measuring the up-conversion emission properties of the materials. The color quality parameters of obtained visible up-conversion emission were also determined as well as possibility of using the Er3 + glasses as erbium doped fiber amplifiers at 1.55 μm in infrared emission region.

The zinc paradigm for metalloneurochemistry.

PubMed

Barr, Chelsea A; Burdette, Shawn C

2017-05-09

Neurotransmission and sensory perception are shaped through metal ion-protein interactions in various brain regions. The term "metalloneurochemistry" defines the unique field of bioinorganic chemistry focusing on these processes, and zinc has been the leading target of metalloneurochemists in the almost 15 years since the definition was introduced. Zinc in the hippocampus interacts with receptors that dictate ion flow and neurotransmitter release. Understanding the intricacies of these interactions is crucial to uncovering the role that zinc plays in learning and memory. Based on receptor similarities and zinc-enriched neurons (ZENs) in areas of the brain responsible for sensory perception, such as the olfactory bulb (OB), and dorsal cochlear nucleus (DCN), zinc participates in odor and sound perception. Development and improvement of methods which allow for precise detection and immediate manipulation of zinc ions in neuronal cells and in brain slices will be critical in uncovering the synaptic action of zinc and, more broadly, the bioinorganic chemistry of cognition. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The zinc spark is an inorganic signature of human egg activation.

PubMed

Duncan, Francesca E; Que, Emily L; Zhang, Nan; Feinberg, Eve C; O'Halloran, Thomas V; Woodruff, Teresa K

2016-04-26

Egg activation refers to events required for transition of a gamete into an embryo, including establishment of the polyspermy block, completion of meiosis, entry into mitosis, selective recruitment and degradation of maternal mRNA, and pronuclear development. Here we show that zinc fluxes accompany human egg activation. We monitored calcium and zinc dynamics in individual human eggs using selective fluorophores following activation with calcium-ionomycin, ionomycin, or hPLCζ cRNA microinjection. These egg activation methods, as expected, induced rises in intracellular calcium levels and also triggered the coordinated release of zinc into the extracellular space in a prominent "zinc spark." The ability of the gamete to mount a zinc spark response was meiotic-stage dependent. Moreover, chelation of intracellular zinc alone was sufficient to induce cell cycle resumption and transition of a meiotic cell into a mitotic one. Together, these results demonstrate critical functions for zinc dynamics and establish the zinc spark as an extracellular marker of early human development.

The zinc spark is an inorganic signature of human egg activation

PubMed Central

Duncan, Francesca E.; Que, Emily L.; Zhang, Nan; Feinberg, Eve C.; O’Halloran, Thomas V.; Woodruff, Teresa K.

2016-01-01

Egg activation refers to events required for transition of a gamete into an embryo, including establishment of the polyspermy block, completion of meiosis, entry into mitosis, selective recruitment and degradation of maternal mRNA, and pronuclear development. Here we show that zinc fluxes accompany human egg activation. We monitored calcium and zinc dynamics in individual human eggs using selective fluorophores following activation with calcium-ionomycin, ionomycin, or hPLCζ cRNA microinjection. These egg activation methods, as expected, induced rises in intracellular calcium levels and also triggered the coordinated release of zinc into the extracellular space in a prominent “zinc spark.” The ability of the gamete to mount a zinc spark response was meiotic-stage dependent. Moreover, chelation of intracellular zinc alone was sufficient to induce cell cycle resumption and transition of a meiotic cell into a mitotic one. Together, these results demonstrate critical functions for zinc dynamics and establish the zinc spark as an extracellular marker of early human development. PMID:27113677

Dual-tail approach to discovery of novel carbonic anhydrase IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site.

PubMed

Hou, Zhuang; Lin, Bin; Bao, Yu; Yan, Hai-Ning; Zhang, Miao; Chang, Xiao-Wei; Zhang, Xin-Xin; Wang, Zi-Jie; Wei, Gao-Fei; Cheng, Mao-Sheng; Liu, Yang; Guo, Chun

2017-05-26

Dual-tail approach was employed to design novel Carbonic Anhydrase (CA) IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site, which also contains a zinc ion as part of the catalytic center. The classic sulfanilamide moiety was used as the zinc binding group. An amino glucosamine fragment was chosen as the hydrophilic part and a cinnamamide fragment as the hydrophobic part in order to draw favorable interactions with the corresponding halves of the active site. In comparison with sulfanilamide which is largely devoid of the hydrophilic and hydrophobic interactions with the two halves of the active site, the compounds so designed and synthesized in this study showed 1000-fold improvement in binding affinity. Most of the compounds inhibited the CA effectively with IC 50 values in the range of 7-152 nM. Compound 14e (IC 50 : 7 nM) was more effective than the reference drug acetazolamide (IC 50 : 30 nM). The results proved that the dual-tail approach to simultaneously matching the hydrophobic and hydrophilic halves of the active site by linking hydrophobic and hydrophilic fragments was useful for designing novel CA inhibitors. The effectiveness of those compounds was elucidated by both the experimental data and molecular docking simulations. This work laid a solid foundation for further development of novel CA IX inhibitors for cancer treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism.

PubMed

Krężel, Artur; Maret, Wolfgang

2017-06-09

Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn 2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn 2+ , the loading of exocytotic vesicles with zinc species, and the control of Zn 2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn 2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn 2+ and Cu⁺ match the biological requirements for controlling-binding and delivering-these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn 2+ and Cu⁺. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

Cadmium and zinc activate adaptive mechanisms in Nicotiana tabacum similar to those observed in metal tolerant plants.

PubMed

Vera-Estrella, Rosario; Gómez-Méndez, María F; Amezcua-Romero, Julio C; Barkla, Bronwyn J; Rosas-Santiago, Paul; Pantoja, Omar

2017-09-01

Tobacco germinated and grew in the presence of high concentrations of cadmium and zinc without toxic symptoms. Evidence suggests that these ions are sequestered into the vacuole by heavy metal/H + exchanger mechanisms. Heavy metal hyperaccumulation and hypertolerance are traits shared by a small set of plants which show specialized physiological and molecular adaptations allowing them to accumulate and sequester toxic metal ions. Nicotiana tabacum was used to test its potential as a metal-accumulator in a glass house experiment. Seed germination was not affected in the presence of increasing concentrations of zinc and cadmium. Juvenile and adult plants could concentrate CdCl 2 and ZnSO 4 to levels exceeding those in the hydroponic growth medium and maintained or increased their leaf dry weight when treated with 0.5- or 1-mM CdCl 2 or 1-mM ZnSO 4 for 5 days. Accumulation of heavy metals did not affect the chlorophyll and carotenoid levels, while variable effects were observed in cell sap osmolarity. Heavy metal-dependent H + transport across the vacuole membrane was monitored using quinacrine fluorescence quenching. Cadmium- or zinc-dependent fluorescence recovery revealed that increasing concentrations of heavy metals stimulated the activities of the tonoplast Cd 2+ or Zn 2+ /H + exchangers. Immunodetection of the V-ATPase subunits showed that the increased proton transport by zinc was not due to changes in protein amount. MTP1 and MTP4 immunodetection and semiquantitative RT-PCR of NtMTP1, NtNRAMP1, and NtZIP1 helped to identify the genes that are likely involved in sequestration of cadmium and zinc in the leaf and root tissue. Finally, we demonstrated that cadmium and zinc treatments induced an accumulation of zinc in leaf tissues. This study shows that N. tabacum possesses a hyperaccumulation response, and thus could be used for phytoremediation purposes.

Co(II) Coordination in Prokaryotic Zinc Finger Domains as Revealed by UV-Vis Spectroscopy.

PubMed

Sivo, Valeria; D'Abrosca, Gianluca; Russo, Luigi; Iacovino, Rosa; Pedone, Paolo Vincenzo; Fattorusso, Roberto; Isernia, Carla; Malgieri, Gaetano

2017-01-01

Co(II) electronic configuration allows its use as a spectroscopic probe in UV-Vis experiments to characterize the metal coordination sphere that is an essential component of the functional structure of zinc-binding proteins and to evaluate the metal ion affinities of these proteins. Here, exploiting the capability of the prokaryotic zinc finger to use different combinations of residues to properly coordinate the structural metal ion, we provide the UV-Vis characterization of Co(II) addition to Ros87 and its mutant Ros87_C27D which bears an unusual CysAspHis 2 coordination sphere. Zinc finger sites containing only one cysteine have been infrequently characterized. We show for the CysAspHis 2 coordination an intense d - d transition band, blue-shifted with respect to the Cys 2 His 2 sphere. These data complemented by NMR and CD data demonstrate that the tetrahedral geometry of the metal site is retained also in the case of a single-cysteine coordination sphere.

Co(II) Coordination in Prokaryotic Zinc Finger Domains as Revealed by UV-Vis Spectroscopy

PubMed Central

Sivo, Valeria; D'Abrosca, Gianluca; Russo, Luigi; Iacovino, Rosa; Pedone, Paolo Vincenzo; Fattorusso, Roberto

2017-01-01

Co(II) electronic configuration allows its use as a spectroscopic probe in UV-Vis experiments to characterize the metal coordination sphere that is an essential component of the functional structure of zinc-binding proteins and to evaluate the metal ion affinities of these proteins. Here, exploiting the capability of the prokaryotic zinc finger to use different combinations of residues to properly coordinate the structural metal ion, we provide the UV-Vis characterization of Co(II) addition to Ros87 and its mutant Ros87_C27D which bears an unusual CysAspHis2 coordination sphere. Zinc finger sites containing only one cysteine have been infrequently characterized. We show for the CysAspHis2 coordination an intense d-d transition band, blue-shifted with respect to the Cys2His2 sphere. These data complemented by NMR and CD data demonstrate that the tetrahedral geometry of the metal site is retained also in the case of a single-cysteine coordination sphere. PMID:29386985

Catalysis by a de novo zinc-mediated protein interface: implications for natural enzyme evolution and rational enzyme engineering.

PubMed

Der, Bryan S; Edwards, David R; Kuhlman, Brian

2012-05-08

Here we show that a recent computationally designed zinc-mediated protein interface is serendipitously capable of catalyzing carboxyester and phosphoester hydrolysis. Although the original motivation was to design a de novo zinc-mediated protein-protein interaction (called MID1-zinc), we observed in the homodimer crystal structure a small cleft and open zinc coordination site. We investigated if the cleft and zinc site at the designed interface were sufficient for formation of a primitive active site that can perform hydrolysis. MID1-zinc hydrolyzes 4-nitrophenyl acetate with a rate acceleration of 10(5) and a k(cat)/K(M) of 630 M(-1) s(-1) and 4-nitrophenyl phosphate with a rate acceleration of 10(4) and a k(cat)/K(M) of 14 M(-1) s(-1). These rate accelerations by an unoptimized active site highlight the catalytic power of zinc and suggest that the clefts formed by protein-protein interactions are well-suited for creating enzyme active sites. This discovery has implications for protein evolution and engineering: from an evolutionary perspective, three-coordinated zinc at a homodimer interface cleft represents a simple evolutionary path to nascent enzymatic activity; from a protein engineering perspective, future efforts in de novo design of enzyme active sites may benefit from exploring clefts at protein interfaces for active site placement.

Influence of active site location on catalytic activity in de novo-designed zinc metalloenzymes.

PubMed

Zastrow, Melissa L; Pecoraro, Vincent L

2013-04-17

While metalloprotein design has now yielded a number of successful metal-bound and even catalytically active constructs, the question of where to put a metal site along a linear, repetitive sequence has not been thoroughly addressed. Often several possibilities in a given sequence may exist that would appear equivalent but may in fact differ for metal affinity, substrate access, or protein dynamics. We present a systematic variation of active site location for a hydrolytically active ZnHis3O site contained within a de novo-designed three-stranded coiled coil. We find that the maximal rate, substrate access, and metal-binding affinity are dependent on the selected position, while catalytic efficiency for p-nitrophenyl acetate hydrolysis can be retained regardless of the location of the active site. This achievement demonstrates how efficient, tailor-made enzymes which control rate, pKa, substrate and solvent access (and selectivity), and metal-binding affinity may be realized. These findings may be applied to the more advanced de novo design of constructs containing secondary interactions, such as hydrogen-bonding channels. We are now confident that changes to location for accommodating such channels can be achieved without location-dependent loss of catalytic efficiency. These findings bring us closer to our ultimate goal of incorporating the secondary interactions we believe will be necessary in order to improve both active site properties and the catalytic efficiency to be competitive with the native enzyme, carbonic anhydrase.

Influence of lead ions on the macromorphology of electrodeposited zinc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuda, Tetsuaki; Tobias, Charles W.

1981-09-01

The morphology of zinc as it is electrodeposited from acid solutions demonstrates a remarkable imprint of electrolyte flow conditions. The development of macromorphology of zinc deposits has been investigated under galvanostatic conditions on a rotating plantinum disk electrode by use of photomacrography, scanning electron microscopy, electron probe microanalysis and Auger microprobe analysis. Logarithmic spiral markings, which reflect the hydrodynamic flow on a rotating disk, appear in a certain region of current density well below the limiting current density. Morphological observations revealed the major influence of trace lead ions on the amplifications of surface roughness through coalescence and preferred growth ofmore » initial protrusions. Results obtained from ultra-pure electrolyte suggest preferred crystal growth towards well-mixed orientation in the concentration field caused by slight differences in crystallization overpotential. A qualitative model involving a coupling mechanism between the evolving surface roughness and instability phenomena in the boundary layer is advanced to explain the formation of spiral patterns.« less

Extracellular zinc and ATP-gated P2X receptor calcium entry channels: New zinc receptors as physiological sensors and therapeutic targets.

PubMed

Schwiebert, Erik M; Liang, Lihua; Cheng, Nai-Lin; Williams, Clintoria Richards; Olteanu, Dragos; Welty, Elisabeth A; Zsembery, Akos

2005-12-01

In this review, we focus on two attributes of P2X receptor channel function, one essential and one novel. First, we propose that P2X receptors are extracellular sensors as well as receptors and ion channels. In particular, the large extracellular domain (that comprises 70% of the molecular mass of the receptor channel protein) lends itself to be a cellular sensor. Moreover, its exquisite sensitivity to extracellular pH, ionic strength, and multiple ligands evokes the function of a sensor. Second, we propose that P2X receptors are extracellular zinc receptors as well as receptors for nucleotides. We provide novel data in multiple publications and illustrative data in this invited review to suggest that zinc triggers ATP-independent activation of P2X receptor channel function. In this light, P2X receptors are the cellular site of integration between autocrine and paracrine zinc signaling and autocrine and paracrine purinergic signaling. P2X receptors may sense changes in these ligands as well as in extracellular pH and ionic strength and transduce these sensations via calcium and/or sodium entry and changes in membrane potential.

Identification of the copper-zinc superoxide dismutase activity in Mycoplasma hyopneumoniae.

PubMed

Chen, J R; Weng, C N; Ho, T Y; Cheng, I C; Lai, S S

2000-05-11

Copper-zinc superoxide dismutase (Cu/ZnSOD), a key enzyme in defense against toxic oxygen-free radicals, is widespread in eukaryotes and several species of gram-negative bacteria. The presence of this enzyme in Mycoplasma hyopneumoniae (M. hyopneumoniae), the primary pathogen of mycoplasmal pneumonia in pigs, was examined since the polyclonal antibody against bovine Cu/ZnSOD was dominantly cross-reactive with the M. hyopneumoniae Cu/ZnSOD from whole cellular proteins. In situ activity staining on SDS-PAGE showed that the molecular mass of M. hyopneumoniae Cu/ZnSOD in reducing form was approximately 17kDa. The presence of Cu and Zn ions at the active site of the enzyme was confirmed on the basis of inhibition by KCN and by H(2)O(2). The activity of M. hyopneumoniae Cu/ZnSOD on both SDS- and native-polyacrylamide gels was completely inhibited by 2mM KCN and the gels showed no iron-containing SOD (FeSOD) or manganese-containing SOD (MnSOD) in the crude extracts. The activity of M. hyopneumoniae Cu/ZnSOD in crude extract was 70units/mg protein and was 55% inhibited by 5mM KCN and 56% inactivated by 40mM H(2)O(2). This enzyme was growth-stage dependent and evidenced markedly higher production during the early log phase. Different expression levels of Cu/ZnSOD activity in field isolates were also detected. Taken together, the presence of Cu/ZnSOD in M. hyopneumoniae was identified for the first time.

Highly Durable Na2V6O16·1.63H2O Nanowire Cathode for Aqueous Zinc-Ion Battery.

PubMed

Hu, Ping; Zhu, Ting; Wang, Xuanpeng; Wei, Xiujuan; Yan, Mengyu; Li, Jiantao; Luo, Wen; Yang, Wei; Zhang, Wencui; Zhou, Liang; Zhou, Zhiqiang; Mai, Liqiang

2018-03-14

Rechargeable aqueous zinc-ion batteries are highly desirable for grid-scale applications due to their low cost and high safety; however, the poor cycling stability hinders their widespread application. Herein, a highly durable zinc-ion battery system with a Na 2 V 6 O 16 ·1.63H 2 O nanowire cathode and an aqueous Zn(CF 3 SO 3 ) 2 electrolyte has been developed. The Na 2 V 6 O 16 ·1.63H 2 O nanowires deliver a high specific capacity of 352 mAh g -1 at 50 mA g -1 and exhibit a capacity retention of 90% over 6000 cycles at 5000 mA g -1 , which represents the best cycling performance compared with all previous reports. In contrast, the NaV 3 O 8 nanowires maintain only 17% of the initial capacity after 4000 cycles at 5000 mA g -1 . A single-nanowire-based zinc-ion battery is assembled, which reveals the intrinsic Zn 2+ storage mechanism at nanoscale. The remarkable electrochemical performance especially the long-term cycling stability makes Na 2 V 6 O 16 ·1.63H 2 O a promising cathode for a low-cost and safe aqueous zinc-ion battery.

Molecular Dynamics Study of Twister Ribozyme: Role of Mg(2+) Ions and the Hydrogen-Bonding Network in the Active Site.

PubMed

Ucisik, Melek N; Bevilacqua, Philip C; Hammes-Schiffer, Sharon

2016-07-12

The recently discovered twister ribozyme is thought to utilize general acid-base catalysis in its self-cleavage mechanism, but the roles of nucleobases and metal ions in the mechanism are unclear. Herein, molecular dynamics simulations of the env22 twister ribozyme are performed to elucidate the structural and equilibrium dynamical properties, as well as to examine the role of Mg(2+) ions and possible candidates for the general base and acid in the self-cleavage mechanism. The active site region and the ends of the pseudoknots were found to be less mobile than other regions of the ribozyme, most likely providing structural stability and possibly facilitating catalysis. A purported catalytic Mg(2+) ion and the closest neighboring Mg(2+) ion remained chelated and relatively immobile throughout the microsecond trajectories, although removal of these Mg(2+) ions did not lead to any significant changes in the structure or equilibrium motions of the ribozyme on the microsecond time scale. In addition, a third metal ion, a Na(+) ion remained close to A1(O5'), the leaving group atom, during the majority of the microsecond trajectories, suggesting that it might stabilize the negative charge on A1(O5') during self-cleavage. The locations of these cations and their interactions with key nucleotides in the active site suggest that they may be catalytically relevant. The P1 stem is partially melted at its top and bottom in the crystal structure and further unwinds in the trajectories. The simulations also revealed an interconnected network comprised of hydrogen-bonding and π-stacking interactions that create a relatively rigid network around the self-cleavage site. The nucleotides involved in this network are among the highly conserved nucleotides in twister ribozymes, suggesting that this interaction network may be important to structure and function.

Inhibition of cyclin-dependent kinase CDK1 by oxindolimine ligands and corresponding copper and zinc complexes.

PubMed

Miguel, Rodrigo Bernardi; Petersen, Philippe Alexandre Divina; Gonzales-Zubiate, Fernando A; Oliveira, Carla Columbano; Kumar, Naresh; do Nascimento, Rafael Rodrigues; Petrilli, Helena Maria; da Costa Ferreira, Ana Maria

2015-10-01

Oxindolimine-copper(II) and zinc(II) complexes that previously have shown to induce apoptosis, with DNA and mitochondria as main targets, exhibit here significant inhibition of kinase CDK1/cyclin B protein. Copper species are more active than the corresponding zinc, and the free ligand shows to be less active, indicating a major influence of coordination in the process, and a further modulation by the coordinated ligand. Molecular docking and classical molecular dynamics provide a better understanding of the effectiveness and kinase inhibition mechanism by these compounds, showing that the metal complex provides a stronger interaction than the free ligand with the ATP-binding site. The metal ion introduces charge in the oxindole species, giving it a more rigid conformation that then becomes more effective in its interactions with the protein active site. Analogous experiments resulted in no significant effect regarding phosphatase inhibition. These results can explain the cytotoxicity of these metal complexes towards different tumor cells, in addition to its capability of binding to DNA, and decreasing membrane potential of mitochondria.

Removal of zinc (II) ion from aqueous solution by adsorption onto activated palm midrib bio-sorbent

NASA Astrophysics Data System (ADS)

Mulana, F.; Mariana; Muslim, A.; Mohibah, M.; Halim, K. H. Ku

2018-03-01

In this paper, palm midrib that was activated with mixed citric acid and tartaric acid as biosorbent was used to remove Zn (II) ion from aqueous solution. The aim of this research is to activate palm midrib by using a mixed citric acid and tartaric acid and to determine adsorption capacity of activated palm midrib biosorbent on Zn (II) ion uptake from aqueous solution. The effect of several parameters such as contact time, initial Zn (II) ion concentration and activator concentration on the degree of Zn (II) ion removal was examined. Atomic Absorption Spectroscopy method was performed to determine adsorbed amount of Zn (II) ion into activated biosorbent. The result showed that the adsorption process was relatively not so fast and equilibrium was reached after contact time of 120 min. The adsorption capacity of biosorbent reached a maximum when the concentration of mixed citric acid and tartaric acid was 1.6 M. The optimum adsorption capacity was 5.72 mg/g. The result was obtained on initial Zn (II) ion concentration of 80 ppm for 120-min contact time. Langmuir isotherm was found as the best fit for the equilibrium data indicating homogeneous adsorption of metal ions onto the biosorbent surface.

Preparation and adsorption characteristics for heavy metals of active silicon adsorbent from leaching residue of lead-zinc tailings.

PubMed

Lei, Chang; Yan, Bo; Chen, Tao; Xiao, Xian-Ming

2018-05-19

To comprehensively reuse the leaching residue obtained from lead-zinc tailings, an active silicon adsorbent (ASA) was prepared from leaching residue and studied as an adsorbent for copper(II), lead(II), zinc(II), and cadmium(II) in this paper. The ASA was prepared by roasting the leaching residue with either a Na 2 CO 3 /residue ratio of 0.6:1 at 700 °C for 1 h or a CaCO 3 /residue ratio of 0.8:1 at 800 °C for 1 h. Under these conditions, the available SiO 2 content of the ASA was more than 20%. The adsorption behaviors of the metal ions onto the ASA were investigated and the Langmuir, Freundlich, and Dubinin-Radushkevich isotherm models were used to analyze the adsorption isotherm. The result showed that the maximum adsorption capacities of copper(II), lead(II), cadmium(II), and zinc(II) calculated by the Langmuir model were 3.40, 2.83, 0.66, and 0.62 mmol g -1 , respectively. The FT-IR spectra of the ASA and the mean free adsorption energies indicated that ion exchange was the mechanism of copper(II), lead(II), and cadmium(II) adsorption and that chemical reaction was the mechanism of zinc(II) adsorption. These results provide a method for reusing the leaching residue obtained from lead-zinc tailings and show that the ASA is an effective adsorbent for heavy metal pollution remediation.

Spectroscopic investigation of zinc tellurite glasses doped with Yb(3+) and Er(3+) ions.

PubMed

Bilir, Gökhan; Kaya, Ayfer; Cinkaya, Hatun; Eryürek, Gönül

2016-08-05

This paper presents a detailed spectroscopic investigation of zinc tellurite glasses with the compositions (0.80-x-y) TeO2+(0.20) ZnO+xEr2O3+yYb2O3 (x=0, y=0; x=0.004, y=0; x=0, y=0.05 and x=0.004, y=0.05 per moles). The samples were synthesized by the conventional melt quenching method. The optical absorption and emission measurements were conducted at room temperature to determine the spectral properties of lanthanides doped zinc tellurite glasses and, to study the energy transfer processes between dopant lanthanide ions. The band gap energies for both direct and indirect possible transitions and the Urbach energies were measured from the absorption spectra. The absorption spectra of the samples were analyzed by using the Judd-Ofelt approach. The effect of the ytterbium ions on the emission properties of erbium ions was investigated and the energy transfer processes between dopant ions were studied by measuring the up-conversion emission properties of the materials. The color quality parameters of obtained visible up-conversion emission were also determined as well as possibility of using the Er(3+) glasses as erbium doped fiber amplifiers at 1.55μm in infrared emission region. Copyright © 2016 Elsevier B.V. All rights reserved.

Different roles of glutathione in copper and zinc chelation in Brassica napus roots.

PubMed

Zlobin, Ilya E; Kartashov, Alexander V; Shpakovski, George V

2017-09-01

We investigated the specific features of copper and zinc excess action on the roots of canola (Brassica napus L.) plants. Copper rapidly accumulated in canola root cells and reached saturation during several hours of treatment, whereas the root zinc content increased relatively slowly. Excessive copper and zinc entry inside the cell resulted in significant cell damage, as evidenced by alterations in plasmalemma permeability and decreases in cellular enzymatic activity. Zinc excess specifically damaged root hair cells, which correlated with a pronounced elevation of their labile zinc level. In vitro, we showed that reduced glutathione (GSH) readily reacted with copper ions to form complexes with blocked sulfhydryl groups. In contrast, zinc ions were ineffective as glutathione blockers, and glutathione molecules did not lose their specific chemical activity in the presence of Zn 2+ ions. The effect of copper and zinc excess on the glutathione pool in canola root cells was analysed by a combination of biochemical determination of total and oxidized glutathione contents and fluorescent staining of free reduced glutathione with monochlorobimane dye. Excess copper led to dose-dependent diminution of free reduced glutathione contents in the root cells, which could not be explained by the loss of total cellular glutathione or its oxidation. In contrast, we observed little effect of much higher intracellular zinc concentrations on the free reduced glutathione content. We concluded that GSH plays an important role in copper excess, but not zinc excess chelation, in canola root cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

H passivation of Li on Zn-site in ZnO: Positron annihilation spectroscopy and secondary ion mass spectrometry

NASA Astrophysics Data System (ADS)

Johansen, K. M.; Zubiaga, A.; Tuomisto, F.; Monakhov, E. V.; Kuznetsov, A. Yu.; Svensson, B. G.

2011-09-01

The interaction of hydrogen (H) with lithium (Li) and zinc vacancies (VZn) in hydrothermally grown n-type zinc oxide (ZnO) has been investigated by positron annihilation spectroscopy (PAS) and secondary ion mass spectrometry. Li on Zn-site (LiZn) is found to be the dominant trap for migrating H atoms, while the trapping efficiency of VZn is considerably smaller. After hydrogenation, where the LiZn acceptor is passivated via formation of neutral LiZn-H pairs, VZn occurs as the prime PAS signature and with a concentration similar to that observed in nonhydrogenated Li-poor samples. Despite a low efficiency as an H trap, the apparent concentration of VZn in Li-poor samples decreases after hydrogenation, as detected by PAS, and evidence for formation of the neutral VZnH2 complex is presented.

Preparation, characterization and bioactivities of Athelia rolfsii exopolysaccharide-zinc complex (AEPS-zinc).

PubMed

Dong, Jinman; Li, Hongmei; Min, Weihong

2018-07-01

A new Athelia rolfsii exopolysaccharides (AEPS) were purified by Sephacryl S-300 and S-200. The physicochemical characteristics of AEPS fractions were assayed by HPGPC and GC methods. The structures of AEPS and AEPS‑zinc complex were characterized by SEM, FTIR and NMR. Moreover, the bioactivities of complex were also evaluated by experiments in vitro and in vivo. AEPSI consisted of glucose, galacturonic acid, talose, galactose, mannose and xylose, the relative contents of them were 24.74, 19.60, 33.65, 8.77, 7.97 and 5.28%, respectively. AEPSII consisted of glucose, inositol, galacturonic acid, ribitol, gluconic acid, talose and xylose, whose relative contents were 36.06, 21.21, 12.78, 11.07, 6.58, 5.45 and 6.82%, respectively. The Mw and Mn of AEPSI were 6.1324×10 4 and 1.4218×10 4 Da, those of AEPSII were 517 and 248Da. SEM observations showed that microstructures of AEPS and AEPS‑zinc complex were obviously different both in size and shape. FTIR and NMR analysis indicated that AEPS might chelate with zinc ion through hydroxy and carboxy group. In vitro experiments showed that AEPS‑zinc complex had a good bioavailability, in vivo experiments showed that it had good effect on improving zinc deficiency and antioxidant activities, which suggested that it could be used as zinc supplementation with high antioxidant activities. Copyright © 2018 Elsevier B.V. All rights reserved.

Improved corrosion resistance on biodegradable magnesium by zinc and aluminum ion implantation

NASA Astrophysics Data System (ADS)

Xu, Ruizhen; Yang, Xiongbo; Suen, Kai Wong; Wu, Guosong; Li, Penghui; Chu, Paul K.

2012-12-01

Magnesium and its alloys have promising applications as biodegradable materials, and plasma ion implantation can enhance the corrosion resistance by modifying the surface composition. In this study, suitable amounts of zinc and aluminum are plasma-implanted into pure magnesium. The surface composition, phases, and chemical states are determined, and electrochemical tests and electrochemical impedance spectroscopy (EIS) are conducted to investigate the surface corrosion behavior and elucidate the mechanism. The corrosion resistance enhancement after ion implantation is believed to stem from the more compact oxide film composed of magnesium oxide and aluminum oxide as well as the appearance of the β-Mg17Al12 phase.

Zinc as a Gatekeeper of Immune Function

PubMed Central

Wessels, Inga; Maywald, Martina; Rink, Lothar

2017-01-01

After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14), zinc “exporters” (ZnT 1–10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate “zinc waves”, and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function. PMID:29186856

Characteristics of Zinc Phosphate Coating Activated by Different Concentrations of Nickel Acetate Solution

NASA Astrophysics Data System (ADS)

Abdalla, Khalid; Zuhailawati, H.; Rahmat, Azmi; Azizan, A.

2017-02-01

Activation pretreatment with nickel acetate solution at various concentrations was performed prior to the phosphating step to enhance the corrosion resistance of carbon steel substrates. The activation solution was studied over various concentrations: 10, 50, and 100 g/L. The effects of these concentrations on surface characteristics and microstructural evolution of the coated samples were characterized by scanning electron microscopy and energy-dispersive spectroscopy. The electrochemical behavior was evaluated using potentiodynamic polarization curves, electrochemical impedance spectroscopy, and immersion test in a 3.5 pct NaCl solution. Significant increases in the nucleation sites and surface coverage of zinc phosphate coating were observed as the concentration of activation solution reached 50 g/L. The electrochemical analysis revealed that the activation treatment with 50 g/L nickel acetate solution significantly improved the protection ability of the zinc phosphate coating. The corrosion current density of activated phosphate coating with 50 g/L was reduced by 64.64 and 13.22 pct, compared to the coatings obtained with activation solutions of 10 and 100 g/L, respectively.

Facilitated Oxygen Chemisorption in Heteroatom-Doped Carbon for Improved Oxygen Reaction Activity in All-Solid-State Zinc-Air Batteries.

PubMed

Liu, Sisi; Wang, Mengfan; Sun, Xinyi; Xu, Na; Liu, Jie; Wang, Yuzhou; Qian, Tao; Yan, Chenglin

2018-01-01

Driven by the intensified demand for energy storage systems with high-power density and safety, all-solid-state zinc-air batteries have drawn extensive attention. However, the electrocatalyst active sites and the underlying mechanisms occurring in zinc-air batteries remain confusing due to the lack of in situ analytical techniques. In this work, the in situ observations, including X-ray diffraction and Raman spectroscopy, of a heteroatom-doped carbon air cathode are reported, in which the chemisorption of oxygen molecules and oxygen-containing intermediates on the carbon material can be facilitated by the electron deficiency caused by heteroatom doping, thus improving the oxygen reaction activity for zinc-air batteries. As expected, solid-state zinc-air batteries equipped with such air cathodes exhibit superior reversibility and durability. This work thus provides a profound understanding of the reaction principles of heteroatom-doped carbon materials in zinc-air batteries. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

PubMed

Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

2018-01-24

Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

Enhancement in ion adsorption rate and desalination efficiency in a capacitive deionization cell through improved electric field distribution using electrodes composed of activated carbon cloth coated with zinc oxide nanorods.

PubMed

Laxman, Karthik; Myint, Myo Tay Zar; Bourdoucen, Hadj; Dutta, Joydeep

2014-07-09

Electrodes composed of activated carbon cloth (ACC) coated with zinc oxide (ZnO) nanorods are compared with plain ACC electrodes, with respect to their desalination efficiency of a 17 mM NaCl solution at different applied potentials. Polarization of the ZnO nanorods increased the penetration depth and strength of the electric field between the electrodes, leading to an increase in the capacitance and charge efficiency at reduced input charge ratios. Uniform distribution of the electric field lines between two electrodes coated with ZnO nanorods led to faster ion adsorption rates, reduced the electrode saturation time, and increased the average desalination efficiency by ∼45% for all applied potentials. The electrodes were characterized for active surface area, capacitance from cyclic voltammetry, theoretical assessment of surface area utilization, and the magnitude of electric field force acting on an ion of unit charge for each potential.

Influence of zinc on bacterial populations and their proteolytic enzyme activities in freshwater environments: a cross-site comparison.

PubMed

Rasmussen, Lauren; Olapade, Ola A

2016-04-01

Temporal responses of indigenous bacterial populations and proteolytic enzyme (i.e., aminopeptidase) activities in the bacterioplankton assemblages from 3 separate freshwater environments were examined after exposure to various zinc (Zn) concentrations under controlled microcosm conditions. Zn concentrations (ranging from 0 to 10 μmol/L) were added to water samples collected from the Kalamazoo River, Rice Creek, and Huron River and examined for bacterial abundance and aminopeptidase activities at various time intervals over a 48 h incubation period in the dark. The results showed that the Zn concentrations did not significantly influence total bacterial counts directly; however, aminopeptidase activities varied significantly to increasing zinc treatments over time. Also, analysis of variance and linear regression analyses revealed significant positive relationships between bacterial numbers and their hydrolytic enzyme activities, suggesting that both probably co-vary with increasing Zn concentrations in aquatic systems. The results from this study serve as additional evidence of the ecological role of Zn as an extracellular peptidase cofactor on the dynamics of bacterial assemblages in aquatic environments.

The effect of Mg dopants on magnetic and structural properties of iron oxide and zinc ferrite thin films

NASA Astrophysics Data System (ADS)

Saritaş, Sevda; Ceviz Sakar, Betul; Kundakci, Mutlu; Yildirim, Muhammet

2018-06-01

Iron oxide thin films have been obtained significant interest as a material that put forwards applications in photovoltaics, gas sensors, biosensors, optoelectronic and especially in spintronics. Iron oxide is one of the considerable interest due to its chemical and thermal stability. Metallic ion dopant influenced superexchange interactions and thus changed the structural, electrical and magnetic properties of the thin film. Mg dopped zinc ferrite (Mg:ZnxFe3-xO4) crystal was used to avoid the damage of Fe3O4 (magnetite) crystal instead of Zn2+ in this study. Because the radius of the Mg2+ ion in the A-site (tetrahedral) is almost equal to that of the replaced Fe3+ ion. Inverse-spinel structure in which oxygen ions (O2-) are arranged to form a face-centered cubic (FCC) lattice where there are two kinds of sublattices, namely, A-site and B-site (octahedral) interstitial sites and in which the super exchange interactions occur. In this study, to increase the saturation of magnetization (Ms) value for iron oxide, inverse-spinal ferrite materials have been prepared, in which the iron oxide was doped by multifarious divalent metallic elements including Zn and Mg. Triple and quaternary; iron oxide and zinc ferrite thin films with Mg metal dopants were grown by using Spray Pyrolysis (SP) technique. The structural, electrical and magnetic properties of Mg dopped iron oxide (Fe2O3) and zinc ferrite (ZnxFe3-xO4) thin films have been investigated. Vibrating Sample Magnetometer (VSM) technique was used to study for the magnetic properties. As a result, we can say that Mg dopped iron oxide thin film has huge diamagnetic and of Mg dopped zinc ferrite thin film has paramagnetic property at bigger magnetic field.

Role of Zinc and Magnesium Ions in the Modulation of Phosphoryl Transfer in Protein Tyrosine Phosphatase 1B.

PubMed

Bellomo, Elisa; Abro, Asma; Hogstrand, Christer; Maret, Wolfgang; Domene, Carmen

2018-03-28

While the majority of phosphatases are metalloenzymes, the prevailing model for the reactions catalyzed by protein tyrosine phosphatases does not involve any metal ion, yet both metal cations and oxoanions affect their enzymatic activity. Mg 2+ and Zn 2+ activate and inhibit, respectively, protein tyrosine phosphatase 1B (PTP1B). Molecular dynamics simulations, metadynamics, and quantum chemical calculations in combination with experimental investigations demonstrate that Mg 2+ and Zn 2+ compete for the same binding site in the active site only in the closed conformation of the enzyme in its phosphorylated state. The two cations have different effects on the arrangements and activities of water molecules that are necessary for the hydrolysis of the phosphocysteine intermediate in the second catalytic step of the reaction. Remarkable differences between the established structural enzymology of PTP1B investigated ex vivo and the function of PTP1B in vivo become evident. Different reaction pathways are viable when the presence of metal ions and their cellular concentrations are considered. The findings suggest that the substrate delivers the inhibitory Zn 2+ ion to the active site. The inhibition and activation can be ascribed to the different coordination chemistries of Zn 2+ and Mg 2+ ions and the orientation of the metal-coordinated water molecules. Metallochemistry adds an additional dimension to the regulation of PTP1B and presumably other members of this enzyme family.

Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

NASA Astrophysics Data System (ADS)

D'Aquino, J. Alejandro; Ringe, Dagmar

2006-08-01

The diphtheria toxin repressor, DtxR, is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear (1 - 3). Calorimetric techniques have demonstrated that while binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 × 10-7, binding site 2 (primary) is a low affinity binding site with a binding constant of 6.3 × 10-4. These two binding sites act independently and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A,C102D), reported here and the previously reported DtxR(H79A) (4) has allowed us to propose a mechanism of metal ion activation for DtxR.

Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment

PubMed Central

Blanchard, Catlyn; Brooks, Lauren; Ebsworth-Mojica, Katherine; Didione, Louis; Wucher, Benjamin; Dewhurst, Stephen; Krysan, Damian

2016-01-01

ABSTRACT Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus are commonly associated with biofilm-associated wound infections that are recalcitrant to conventional antibiotics. As an initial means to identify agents that may have a greater propensity to improve clearance of wound-associated bacterial pathogens, we screened a Food and Drug Administration-approved drug library for members that display bactericidal activity toward 72-h-established P. aeruginosa biofilms using an adenylate kinase reporter assay for bacterial cell death. A total of 34 compounds displayed antibiofilm activity. Among these, zinc pyrithione was also shown to reduce levels of A. baumannii and S. aureus biofilm-associated bacteria and exhibited an additive effect in combination with silver sulfadiazine, a leading topical therapeutic for wound site infections. The improved antimicrobial activity of zinc pyrithione and silver sulfadiazine was maintained in an ointment formulation and led to improved clearance of P. aeruginosa, A. baumannii, and S. aureus in a murine model of wound infection. Taken together, these results suggest that topical zinc pyrithione and silver sulfadiazine combination formulations may mitigate wound-associated bacterial infections and disease progression. IMPORTANCE Topical antimicrobial ointments ostensibly mitigate bacterial wound disease and reliance on systemic antibiotics. Yet studies have called into question the therapeutic benefits of several traditional topical antibacterials, accentuating the need for improved next-generation antimicrobial ointments. Yet the development of such agents consisting of a new chemical entity is a time-consuming and expensive proposition. Considering that drug combinations are a mainstay therapeutic strategy for the treatment of other therapeutic indications, one alternative approach is to improve the performance of conventional antimicrobial ointments by the addition of a well-characterized and FDA

Modification of optical and electrical properties of zinc oxide-coated porous silicon nanostructures induced by swift heavy ion

PubMed Central

2012-01-01

Morphological and optical characteristics of radio frequency-sputtered zinc aluminum oxide over porous silicon (PS) substrates were studied before and after irradiating composite films with 130 MeV of nickel ions at different fluences varying from 1 × 1012 to 3 × 1013 ions/cm2. The effect of irradiation on the composite structure was investigated by scanning electron microscopy, X-ray diffraction (XRD), photoluminescence (PL), and cathodoluminescence spectroscopy. Current–voltage characteristics of ZnO-PS heterojunctions were also measured. As compared to the granular crystallites of zinc oxide layer, Al-doped zinc oxide (ZnO) layer showed a flaky structure. The PL spectrum of the pristine composite structure consists of the emission from the ZnO layer as well as the near-infrared emission from the PS substrate. Due to an increase in the number of deep-level defects, possibly oxygen vacancies after swift ion irradiation, PS-Al-doped ZnO nanocomposites formed with high-porosity PS are shown to demonstrate a broadening in the PL emission band, leading to the white light emission. The broadening effect is found to increase with an increase in the ion fluence and porosity. XRD study revealed the relative resistance of the film against the irradiation, i.e., the irradiation of the structure failed to completely amorphize the structure, suggesting its possible application in optoelectronics and sensing applications under harsh radiation conditions. PMID:22748164

Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme.

PubMed Central

Hermann, T; Auffinger, P; Scott, W G; Westhof, E

1997-01-01

In the presence of magnesium ions, cleavage by the hammerhead ribozyme RNA at a specific residue leads to 2'3'-cyclic phosphate and 5'-OH extremities. In the cleavage reaction an activated ribose 2'-hydroxyl group attacks its attached 3'-phosphate. Molecular dynamics simulations of the crystal structure of the hammerhead ribozyme, obtained after flash-freezing of crystals under conditions where the ribozyme is active, provide evidence that a mu-bridging OH-ion is located between two Mg2+ions close to the cleavable phosphate. Constrained simulations show further that a flip from the C3'- endo to the C2'- endo conformation of the ribose at the cleavable phosphate brings the 2'-hydroxyl in proximity to both the attacked phosphorous atom and the mu-bridging OH-ion. Thus, the simulations lead to a detailed new insight into the mechanism of hammerhead ribozyme cleavage where a mu-hydroxo bridged magnesium cluster, located on the deep groove side, provides an OH-ion that is able to activate the 2'-hydroxyl nucleophile after a minor and localized conformational change in the RNA. PMID:9254698

Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc.

PubMed

Anderson, Charles T; Radford, Robert J; Zastrow, Melissa L; Zhang, Daniel Y; Apfel, Ulf-Peter; Lippard, Stephen J; Tzounopoulos, Thanos

2015-05-19

Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling.

Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc

PubMed Central

Anderson, Charles T.; Radford, Robert J.; Zastrow, Melissa L.; Zhang, Daniel Y.; Apfel, Ulf-Peter; Lippard, Stephen J.; Tzounopoulos, Thanos

2015-01-01

Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling. PMID:25947151

Solution NMR Refinement of a Metal Ion Bound Protein Using Metal Ion Inclusive Restrained Molecular Dynamics Methods

PubMed Central

Chakravorty, Dhruva K.; Wang, Bing; Lee, Chul Won; Guerra, Alfredo J.; Giedroc, David P.; Merz, Kenneth M.

2013-01-01

Correctly calculating the structure of metal coordination sites in a protein during the process of nuclear magnetic resonance (NMR) structure determination and refinement continues to be a challenging task. In this study, we present an accurate and convenient means by which to include metal ions in the NMR structure determination process using molecular dynamics (MD) constrained by NMR-derived data to obtain a realistic and physically viable description of the metal binding site(s). This method provides the framework to accurately portray the metal ions and its binding residues in a pseudo-bond or dummy-cation like approach, and is validated by quantum mechanical/molecular mechanical (QM/MM) MD calculations constrained by NMR-derived data. To illustrate this approach, we refine the zinc coordination complex structure of the zinc sensing transcriptional repressor protein Staphylococcus aureus CzrA, generating over 130 ns of MD and QM/MM MD NMR-data compliant sampling. In addition to refining the first coordination shell structure of the Zn(II) ion, this protocol benefits from being performed in a periodically replicated solvation environment including long-range electrostatics. We determine that unrestrained (not based on NMR data) MD simulations correlated to the NMR data in a time-averaged ensemble. The accurate solution structure ensemble of the metal-bound protein accurately describes the role of conformational dynamics in allosteric regulation of DNA binding by zinc and serves to validate our previous unrestrained MD simulations of CzrA. This methodology has potentially broad applicability in the structure determination of metal ion bound proteins, protein folding and metal template protein-design studies. PMID:23609042

Ion Selectivity in the KcsA Potassium Channel from the Perspective of the Ion Binding Site

PubMed Central

Dixit, Purushottam D.; Merchant, Safir; Asthagiri, D.

2009-01-01

To understand the thermodynamic exclusion of Na+ relative to K+ from the S2 site of the selectivity filter, the distribution PX(ɛ) (X = K+ or Na+) of the binding energy (ɛ) of the ion with the channel is analyzed using the potential distribution theorem. By expressing the excess chemical potential of the ion as a sum of mean-field 〈ɛ〉 and fluctuation μexflux,X contributions, we find that selectivity arises from a higher value of μflux,Na+ex relative to μflux,K+ex. To understand the role of site-site interactions on μexflux,X, we decompose PX(ɛ) into n-dependent distributions, where n is the number of ion-coordinating ligands within a distance λ from the ion. For λ comparable to typical ion-oxygen bond distances, investigations building on this multistate model reveal an inverse correlation between favorable ion-site and site-site interactions: the ion-coordination states that most influence the thermodynamics of the ion are also those for which the binding site is energetically less strained and vice versa. This correlation motivates understanding entropic effects in ion binding to the site and leads to the finding that μexflux,X is directly proportional to the average site-site interaction energy, a quantity that is sensitive to the chemical type of the ligand coordinating the ion. Increasing the coordination number around Na+ only partially accounts for the observed magnitude of selectivity; acknowledging the chemical type of the ion-coordinating ligand is essential. PMID:19289040

Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8.

PubMed

Eron, Scott J; MacPherson, Derek J; Dagbay, Kevin B; Hardy, Jeanne A

2018-05-18

Zinc is emerging as a widely used and important biological regulatory signal. Cellular zinc levels are tightly regulated by a complex array of zinc importers and exporters to control processes such as apoptotic cell death. While caspase inhibition by zinc has been reported previously, the reported inhibition constants were too weak to suggest a critical biological role for zinc-mediated inhibition. In this work, we have adopted a method of assessing available zinc. This allowed assessment of accurate inhibition constants for apoptotic caspases, caspase-3, -6, -7, and -8. Each of these caspases are inhibited by zinc at intracellular levels but with widely differing inhibition constants and different zinc binding stoichiometries. Caspase-3, -6, and -8 appear to be constitutively inhibited by typical zinc levels, and this inhibition must be lifted to allow activation. The inhibition constant for caspase-7 (76 nM) is much weaker than for the other apoptotic caspases (2.6-6.9 nM) suggesting that caspase-7 is not inactivated by normal zinc concentrations but can be inhibited under conditions of zinc stress. Caspase-3, -7, and -8 were found to bind three, one, and two zincs, respectively. In each of these caspases, zinc was present in the active site, in contrast to caspase-6, which binds one zinc allosterically. The most notable new mechanism to emerge from this work is for zinc-mediated inhibition of caspase-8. Zinc binds caspase-8 directly at the active site and at a second site. Zinc binding inhibits formation of the caspase-8 dimer, the activated form of the enzyme. Together these findings suggest that zinc plays a critical role in regulation of apoptosis by direct inactivation of caspases, in a manner that is unique for each caspase.

Molecular basis for subtype-specificity and high-affinity zinc inhibition in the GluN1-GluN2A NMDA receptor amino terminal domain

PubMed Central

Romero-Hernandez, Annabel; Simorowski, Noriko; Karakas, Erkan

2016-01-01

Summary Zinc is vastly present in the mammalian brain and controls functions of various cell surface receptors to regulate neurotransmission. A distinctive characteristic of N-methyl-D-aspartate (NMDA) receptors containing a GluN2A subunit is that their ion channel activity is allosterically inhibited by a nano-molar concentration of zinc that binds to an extracellular domain called an amino terminal domain (ATD). Despite physiological importance, the molecular mechanism underlying the high-affinity zinc inhibition has been incomplete due to lack of a GluN2A ATD structure. Here we show the first crystal structures of the heterodimeric GluN1-GluN2A ATD, which provide the complete map of the high-affinity zinc binding site and reveals distinctive features from the ATD of the GluN1-GluN2B subtype. Perturbation of hydrogen bond networks at the hinge of the GluN2A bi-lobe structure affects both zinc inhibition and open probability supporting the general model where the bi-lobe motion in ATD regulates the channel activity in NMDA receptors. PMID:27916457

Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.

PubMed

Kogan, Samuel; Sood, Aditya; Garnick, Mark S

2017-04-01

Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.

Enhanced antibacterial activity and biocompatibility of zinc-incorporated organic-inorganic nanocomposite coatings via electrophoretic deposition.

PubMed

Huang, Pin; Ma, Kena; Cai, Xinjie; Huang, Dan; Yang, Xu; Ran, Jiabing; Wang, Fushi; Jiang, Tao

2017-12-01

Increased use of reconstruction procedures in orthopedics has improved the life of patients undergoing surgery. However, surgical site infection remains a major challenge. Efforts were made to fabricate antibacterial surfaces with good biocompatibility. This present study aimed to fabricate zinc-incorporated chitosan/gelatin (CS/G) nanocomposite coatings on the titanium substrates via electrophoretic deposition (EPD). Physicochemical characterization confirmed that zinc was successfully deposited in a metallic oxide/salt complex status. Transmission electron microscopic (TEM) results observed formation of core-shell nanosized particles released from the coatings. The selected-area electron diffraction (SAED) pattern of the particles presented faces of ZnO with organic background. Mechanical tests showed improved tensile and shear bond strength between substrates and zinc-incorporated coating surfaces. Zinc-incorporated CS/G coatings presented antibacterial abilities against both Gram-negative E. coli and Gram-positive S. aureus in a concentration-dependent manner. The generation of ZnO/Zn 2+ complex in the coatings may contribute to bacteria inhibition. In vitro study demonstrated that appropriate concentration of zinc could promote proliferative and osteogenic activities of rat bone marrow stromal cells. The present study suggested that zinc-incorporated CS/G coating was a promising candidate for surface modification of biomedical materials. Copyright © 2017 Elsevier B.V. All rights reserved.

Chromium Ions in Tetrahedral Sites

DTIC Science & Technology

1991-09-01

octahedral sites-the inversion site and the mirror site.4 After energy level calculations were performed, it was found that chromium ions in octahedral sites...octahedral site with symmetry C, the other half at the mirror octahedral sites with symmetry Cs. Its structure projected on (100) plane is shown in Fig... mirror symmetry. I 181 !U 10O 0 0 Fig. 2.1 Unit cell of forsterite, Mg2SiO4. Small open and solid circles are Mg atoms, big circles are 0 atoms and

Enhancement of hippocampal mossy fiber activity in zinc deficiency and its influence on behavior.

PubMed

Takeda, Atsushi; Itoh, Hiromasa; Yamada, Kohei; Tamano, Haruna; Oku, Naoto

2008-10-01

The extracellular concentration of glutamate in the hippocampus is increased by hippocampal perfusion with CaEDTA, a membrane-impermeable zinc chelator, suggesting that the activity of glutamatergic neurons in the hippocampus are influenced by the extracellular concentrations of zinc. In the present study, the relationship between the extracellular concentrations of zinc and mossy fiber activity in the hippocampus was examined in mice and rats fed a zinc-deficient diet for 4 weeks. Timm's stain, by which histochemically reactive zinc in the presynaptic vesicles is detected, was attenuated in the hippocampus in zinc deficiency. The extracellular signal of ZnAF-2, a membrane-impermeable zinc indicator, was also lower in the hippocampal CA3, suggesting that the basal extracellular concentrations of zinc are lower maintained in zinc deficiency. To check mossy fiber activity after 4-week zinc deprivation, the decrease in the signal of FM4-64, an indicator of presynaptic activity (exocytosis), at mossy fiber synapses was measured under the condition of spontaneous depolarization. The decrease was significantly facilitated by zinc deficiency, suggesting that the basal exocytosis at mossy fiber synapses is enhanced by zinc deficiency. On the other hand, the increase in anxiety-like behavior was observed in the open-field test after 4-week zinc deprivation. The present study demonstrates that the decrease in the basal extracellular concentrations of zinc may be linked to the enhancement of the basal mossy fiber activity in zinc deficiency. This decrease seems to be also involved in neuropsychological behavior in zinc deficiency.

Accumulation of metals in fish from lead-zinc mining areas of southeastern Missouri, USA

USGS Publications Warehouse

Schmitt, Christopher J.; Brumbaugh, William G.; May, Thomas W.

2007-01-01

The potential effects of proposed lead-zinc mining in an ecologically sensitive area were assessed by studying a nearby mining district that has been exploited for about 30 yr under contemporary environmental regulations and with modern technology. Blood and liver samples representing fish of three species (largescale stoneroller, Campostoma oligolepis, n=91; longear sunfish, Lepomis megalotis, n=105; and northern hog sucker, Hypentelium nigricans, n=20) were collected from 16 sites representing a range of conditions relative to lead-zinc mining and ore beneficiation in southeastern Missouri. Samples were analyzed for lead, zinc, and cadmium, and for a suite of biomarkers (reported in a companion paper). A subset of the hog sucker (n=9) representing three sites were also analyzed for nickel and cobalt. Blood and liver lead concentrations were highly correlated (r=0.84-0.85, P < 0.01) in all three species and were significantly (ANOVA, P < 0.01) greater at sites < 10 km downstream of active lead-zinc mines and mills and in a historical lead-zinc mining area than at reference sites, including a site in the area proposed for new mining. Correlations between blood and liver cadmium concentrations were less evident than for lead but were nevertheless statistically significant (r=0.26-0.69, P < 0.01-0.07). Although blood and liver cadmium concentrations were highest in all three species at sites near mines, within-site variability was greater and mining-related trends were less evident than for lead. Blood and liver zinc concentrations were significantly correlated only in stoneroller (r=0.46, P < 0.01) and mining-related trends were not evident. Concentrations of cobalt and nickel in blood and liver were significantly higher (ANOVA, P < 0.01) at a site near an active mine than at a reference site and a site in the historical lead-zinc mining area. These findings confirm previous studies indicating that lead and other metals are released to streams from active lead-zinc

Accumulation of metals in fish from lead-zinc mining areas of southeastern Missouri, USA.

PubMed

Schmitt, Christopher J; Brumbaugh, William G; May, Thomas W

2007-05-01

The potential effects of proposed lead-zinc mining in an ecologically sensitive area were assessed by studying a nearby mining district that has been exploited for about 30 yr under contemporary environmental regulations and with modern technology. Blood and liver samples representing fish of three species (largescale stoneroller, Campostoma oligolepis, n=91; longear sunfish, Lepomis megalotis, n=105; and northern hog sucker, Hypentelium nigricans, n=20) were collected from 16 sites representing a range of conditions relative to lead-zinc mining and ore beneficiation in southeastern Missouri. Samples were analyzed for lead, zinc, and cadmium, and for a suite of biomarkers (reported in a companion paper). A subset of the hog sucker (n=9) representing three sites were also analyzed for nickel and cobalt. Blood and liver lead concentrations were highly correlated (r=0.84-0.85, P<0.01) in all three species and were significantly (ANOVA, P<0.01) greater at sites <10 km downstream of active lead-zinc mines and mills and in a historical lead-zinc mining area than at reference sites, including a site in the area proposed for new mining. Correlations between blood and liver cadmium concentrations were less evident than for lead but were nevertheless statistically significant (r=0.26-0.69, P <0.01-0.07). Although blood and liver cadmium concentrations were highest in all three species at sites near mines, within-site variability was greater and mining-related trends were less evident than for lead. Blood and liver zinc concentrations were significantly correlated only in stoneroller (r=0.46, P<0.01) and mining-related trends were not evident. Concentrations of cobalt and nickel in blood and liver were significantly higher (ANOVA, P<0.01) at a site near an active mine than at a reference site and a site in the historical lead-zinc mining area. These findings confirm previous studies indicating that lead and other metals are released to streams from active lead-zinc mines and

Assessment of copper, cadmium and zinc remobilization in Mediterranean marine coastal sediments

NASA Astrophysics Data System (ADS)

Sakellari, Aikaterini; Plavšić, Marta; Karavoltsos, Sotiris; Dassenakis, Manos; Scoullos, Michael

2011-01-01

The remobilization of copper, cadmium and zinc in sediments of three selected coastal microenvironments of the Aegean Sea (Eastern Mediterranean) is assessed. Various analytical methods and techniques were employed providing concentrations, profiles and forms of metals and organic matter in sediments and pore waters. At Loutropyrgos, a non-industrial site located, however, within an intensively industrialized enclosed gulf, an intense resupply of zinc in pore water from sediment was recorded, correlating with the highest value of weakly bound fraction of zinc determined at this area. The comparatively high zinc concentrations measured in the pore waters (394 nM), exceed considerably those in the overlying seawater (12.5 nM determined by DGT; 13.5 nM total), resulting in the formation of a strong concentration gradient at the sediment-water interface. Potential zinc flux at the sediment-water interface at Loutropyrgos (based on 0.4 mm DGT profile) was calculated equal to 0.8 mmol.m -2.d -1. The half lives of trace metals at Loutropyrgos site, based on the aforementioned DGT profiles, amount to 0.1 y (Zn), 2.8 y (Cd), 4.5 y (Cu), 2.2 y (Mn) and 0.4 y (Fe) pointing out to the reactivity of these metals at the sediment-water interface. The concentration of dissolved organic carbon (DOC) in pore waters of the three selected sites (2.7-5.2 mg/L) was up to four times higher compared to that of the corresponding overlying seawater. Similarly, the concentrations of carbohydrates in pore waters (0.20-0.91 mg/L monosaccharides; 0.71-1.6 mg/L polysaccharides) are an order of magnitude higher than those of seawater, forming a concentration gradient at the sediment-water interface. Total carbohydrates contribute between 34 and 48% of the organic carbon of the pore waters, being significantly higher than those of seawater from the corresponding areas, which were in the range of 15-21%. The complexing capacity as for copper ions (CCu) determined in pore water ranges widely, from 0

Essential role for zinc-triggered p75NTR activation in preconditioning neuroprotection.

PubMed

Lee, Jin-Yeon; Kim, Yu-Jin; Kim, Tae-Youn; Koh, Jae-Young; Kim, Yang-Hee

2008-10-22

Ischemic preconditioning (PC) of the brain is a phenomenon by which mild ischemic insults render neurons resistant to subsequent strong insults. Key steps in ischemic PC of the brain include caspase-3 activation and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, but upstream events have not been clearly elucidated. We have tested whether endogenous zinc is required for ischemic PC of the brain in rats. Mild, transient zinc accumulation was observed in certain neurons after ischemic PC. Moreover, intraventricular administration of CaEDTA during ischemic PC abrogated both zinc accumulation and the protective effect against subsequent full ischemia. To elucidate the mechanism of the zinc-triggered PC (Zn PC) effect, cortical cultures were exposed to sublethal levels of zinc, and 18 h later to lethal levels of zinc or NMDA. Zn PC exhibited the characteristic features of ischemic PC, including caspase-3 activation, PARP-1 cleavage, and HSP70 induction, all of which are crucial for subsequent neuroprotection against NMDA or zinc toxicity. HSP70 induction was necessary for protection, as it halted caspase-3 activation before apoptosis. Interestingly, in both Zn PC in vitro and ischemic PC in vivo, p75(NTR) was necessary for neuroprotection. These results suggest that caspase-3 activation during ischemic PC, a necessary event for subsequent neuroprotection, may result from mild zinc accumulation and the consequent p75(NTR) activation in neurons.

Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells.

PubMed

Guo, Dadong; Bi, Hongsheng; Wang, Daoguang; Wu, Qiuxin

2013-08-01

Zinc oxide nanoparticle is one of the most important materials with diverse applications. However, it has been reported that zinc oxide nanoparticles are toxic to organisms, and that oxidative stress is often hypothesized to be an important factor in cytotoxicity mediated by zinc oxide nanoparticles. Nevertheless, the mechanism of toxicity of zinc oxide nanoparticles has not been completely understood. In this study, we investigated the cytotoxic effect of zinc oxide nanoparticles and the possible molecular mechanism involved in calcium homeostasis mediated by plasma membrane calcium ATPase in rat retinal ganglion cells. Real-time cell electronic sensing assay showed that zinc oxide nanoparticles could exert cytotoxic effect on rat retinal ganglion cells in a concentration-dependent manner; flow cytometric analysis indicated that zinc oxide nanoparticles could lead to cell damage by inducing the overproduction of reactive oxygen species. Furthermore, zinc oxide nanoparticles could also apparently decrease the expression level and their activity of plasma membrane calcium ATPase, which finally disrupt the intracellular calcium homeostasis and result in cell death. Taken together, zinc oxide nanoparticles could apparently decrease the plasma membrane calcium ATPase expression, inhibit their activity, cause the elevated intracellular calcium ion level and disrupt the intracellular calcium homeostasis. Further, the disrupted calcium homeostasis will trigger mitochondrial dysfunction, generate excessive reactive oxygen species, and finally initiate cell death. Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

Zinc stimulates glucose oxidation and glycemic control by modulating the insulin signaling pathway in human and mouse skeletal muscle cell lines.

PubMed

Norouzi, Shaghayegh; Adulcikas, John; Sohal, Sukhwinder Singh; Myers, Stephen

2018-01-01

Zinc is a metal ion that is an essential cell signaling molecule. Highlighting this, zinc is an insulin mimetic, activating cellular pathways that regulate cellular homeostasis and physiological responses. Previous studies have linked dysfunctional zinc signaling with several disease states including cancer, obesity, cardiovascular disease and type 2 diabetes. The present study evaluated the insulin-like effects of zinc on cell signaling molecules including tyrosine, PRSA40, Akt, ERK1/2, SHP-2, GSK-3β and p38, and glucose oxidation in human and mouse skeletal muscle cells. Insulin and zinc independently led to the phosphorylation of these proteins over a 60-minute time course in both mouse and human skeletal muscle cells. Similarly, utilizing a protein array we identified that zinc could active the phosphorylation of p38, ERK1/2 and GSK-3B in human and ERK1/2 and GSK-3B in mouse skeletal muscle cells. Glucose oxidation assays were performed on skeletal muscle cells treated with insulin, zinc, or a combination of both and resulted in a significant induction of glucose consumption in mouse (p<0.01) and human (p<0.05) skeletal muscle cells when treated with zinc alone. Insulin, as expected, increased glucose oxidation in mouse (p<0.001) and human (0.001) skeletal muscle cells, however the combination of zinc and insulin did not augment glucose consumption in these cells. Zinc acts as an insulin mimetic, activating key molecules implicated in cell signaling to maintain glucose homeostasis in mouse and human skeletal muscle cells. Zinc is an important metal ion implicated in several biological processes. The role of zinc as an insulin memetic in activating key signaling molecules involved in glucose homeostasis could provide opportunities to utilize this ion therapeutically in treating disorders associated with dysfunctional zinc signaling.

Zinc stress induces copper depletion in Acinetobacter baumannii.

PubMed

Hassan, Karl A; Pederick, Victoria G; Elbourne, Liam D H; Paulsen, Ian T; Paton, James C; McDevitt, Christopher A; Eijkelkamp, Bart A

2017-03-11

The first row transition metal ions zinc and copper are essential to the survival of many organisms, although in excess these ions are associated with significant toxicity. Here, we examined the impact of zinc and copper stress on Acinetobacter baumannii, a common opportunistic pathogen. We show that extracellular zinc stress induces a copper-specific depletion phenotype in A. baumannii ATCC 17978. Supplementation with copper not only fails to rescue this phenotype, but further exacerbates the copper depletion. Extensive analysis of the A. baumannii ATCC 17978 genome identified 13 putative zinc/copper resistance efflux pumps. Transcriptional analyses show that four of these transporters are responsive to zinc stress, five to copper stress and seven to the combination of zinc and copper stress, thereby revealing a likely foundation for the zinc-induced copper starvation in A. baumannii. In addition, we show that zinc and copper play crucial roles in management of oxidative stress and the membrane composition of A. baumannii. Further, we reveal that zinc and copper play distinct roles in macrophage-mediated killing of this pathogen. Collectively, this study supports the targeting of metal ion homeostatic mechanisms as an effective antimicrobial strategy against multi-drug resistant bacterial pathogens.

Transcriptome sequencing and analysis of zinc-uptake-related genes in Trichophyton mentagrophytes.

PubMed

Zhang, Xinke; Dai, Pengxiu; Gao, Yongping; Gong, Xiaowen; Cui, Hao; Jin, Yipeng; Zhang, Yihua

2017-11-21

Trichophyton mentagrophytes is an important zoonotic dermatophytic (ringworm) pathogen; causing severe skin infection in humans and other animals worldwide. Fortunately, commonly used fungal skin disease prevention and treatment measures are relatively simple. However, T. mentagrophytes is primarily studied at the epidemiology and drug efficacy research levels, yet current study has been unable to meet the needs of clinical medicine. Zinc is a crucial trace element for the growth and reproduction of fungi and other microorganisms. The metal ions coordinate within a variety of proteins to form zinc finger proteins, which perform many vital biological functions. Zinc transport regulatory networks have not been resolved in T. mentagrophytes. The T. mentagrophytes transcriptome will allow us to discover new genes, particularly those genes involved in zinc uptake. We found T. mentagrophytes growth to be restricted by zinc deficiency; natural T. mentagrophytes growth requires zinc ions. T. Mentagrophytes must acquire zinc ions for growth and development. The transcriptome of T. mentagrophytes was sequenced by using Illumina HiSeq™ 2000 technology and the de novo assembly of the transcriptome was performed by using the Trinity method, and functional annotation was analyzed. We got 10,751 unigenes. The growth of T. mentagrophytes is severely inhibited and there were many genes showing significant up regulation and down regulation respectively in T. mentagrophytes when zinc deficiency. Zinc deficiency can affect the expression of multiple genes of T. mentagrophytes. The effect of the zinc deficiency could be recovered in the normal medium. And we finally found the zinc-responsive activating factor (ZafA) and speculated that 4 unigenes are zinc transporters. We knocked ZafA gene by ATMT transformation in T. mentagrophytes, the result showed that ZafA gene is very important for the growth and the generation of conidia in T. mentagrophytes. The expression of 4 zinc

Alterations in protein kinase C activity and processing during zinc-deficiency-induced cell death.

PubMed

Chou, Susan S; Clegg, Michael S; Momma, Tony Y; Niles, Brad J; Duffy, Jodie Y; Daston, George P; Keen, Carl L

2004-10-01

Protein kinases C (PKCs) are a family of serine/threonine kinases that are critical for signal transduction pathways involved in growth, differentiation and cell death. All PKC isoforms have four conserved domains, C1-C4. The C1 domain contains cysteine-rich finger-like motifs, which bind two zinc atoms. The zinc-finger motifs modulate diacylglycerol binding; thus, intracellular zinc concentrations could influence the activity and localization of PKC family members. 3T3 cells were cultured in zinc-deficient or zinc-supplemented medium for up to 32 h. Cells cultured in zinc-deficient medium had decreased zinc content, lowered cytosolic classical PKC activity, increased caspase-3 processing and activity, and reduced cell number. Zinc-deficient cytosols had decreased activity and expression levels of PKC-alpha, whereas PKC-alpha phosphorylation was not altered. Inhibition of PKC-alpha with Gö6976 had no effect on cell number in the zinc-deficient group. Proteolysis of the novel PKC family member, PKC-delta, to its 40-kDa catalytic fragment occurred in cells cultured in the zinc-deficient medium. Occurrence of the PKC-delta fragment in mitochondria was co-incident with caspase-3 activation. Addition of the PKC-delta inhibitor, rottlerin, or zinc to deficient medium reduced or eliminated proteolysis of PKC-delta, activated caspase-3 and restored cell number. Inhibition of caspase-3 processing by Z-DQMD-FMK (Z-Asp-Gln-Met-Asp-fluoromethylketone) did not restore cell number in the zinc-deficient group, but resulted in processing of full-length PKC-delta to a 56-kDa fragment. These results support the concept that intracellular zinc concentrations influence PKC activity and processing, and that zinc-deficiency-induced apoptosis occurs in part through PKC-dependent pathways.

Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Aquino,J.; Tetenbaum-Novatt, J.; White, A.

2005-01-01

The diphtheria toxin repressor (DtxR) is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear. Calorimetric techniques have demonstrated that although binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 x 10{sup -7}, binding site 2 (primary) is a low-affinity binding site with amore » binding constant of 6.3 x 10{sup -4}. These two binding sites act in an independent fashion, and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A, C102D), reported here, and the previously reported DtxR(H79A) have allowed us to propose a mechanism of metal activation for DtxR.« less

Structural relatedness of three ion-transport adenosine triphosphatases around their active sites of phosphorylation.

PubMed

Walderhaug, M O; Post, R L; Saccomani, G; Leonard, R T; Briskin, D P

1985-03-25

Three membrane-bound adenosine triphosphatases were investigated for homology in the sequence of four amino acids about the active site of phosphorylation. The ATPases were as follows: sodium-potassium-dependent ATPase from dog kidney, Na,K-ATPase; hydrogen-potassium-dependent ATPase from hog gastric mucosa, H,K-ATPase, an ATPase similar to Na,K-ATPase; and an ATPase activity in the plasma membrane of corn, Zea mays, roots (CR-ATPase), a higher plant ATPase. A membrane preparation containing an ATPase of Acholeplasma laidlawii, a prokaryote, (AL) was also investigated. For most of the experiments, the preparations were phosphorylated from [gamma-32P]ATP, denatured in acid, and subjected to proteolytic digestion. Radioactive phosphopeptides were separated by high voltage paper electrophoresis and characterized by sensitivity to chemical reagents. In gastric H,K-ATPase, the aspartate residue at the active site was determined directly by labeling with [3H]borohydride. A common sequence around the active site was found for Na,K-ATPase, H,K-ATPase, and CR-ATPase. This sequence, -Cys-(Ser/Thr)-Asp(P)-Lys-, is similar to that in the calcium ion-transport ATPase of sarcoplasmic reticulum. The AL membrane preparation showed an acylphosphate that turned over rapidly after a chase of labeled membranes with unlabeled ATP. The corresponding sequence was different from that of the three ATPases. An acylphosphate was on two polypeptides with molecular weights of about 80,000 and 60,000; these appear not to correspond to subunits of a Na+-stimulated ATPase in this organism (Lewis, R. N. A. H., and McElhaney, R. N. (1983) Biochim. Biophys. Acta 735, 113-122).

Characterizing multiple metal ion binding sites within a ribozyme by cadmium-induced EPR silencing

PubMed Central

Kisseleva, Natalia; Kraut, Stefanie; Jäschke, Andres; Schiemann, Olav

2007-01-01

In ribozyme catalysis, metal ions are generally known to make structural and∕or mechanistic contributions. The catalytic activity of a previously described Diels-Alderase ribozyme was found to depend on the concentration of divalent metal ions, and crystallographic data revealed multiple binding sites. Here, we elucidate the interactions of this ribozyme with divalent metal ions in solution using electron paramagnetic resonance (EPR) spectroscopy. Manganese ion titrations revealed five high-affinity Mn2+ binding sites with an upper Kd of 0.6±0.2 μM. In order to characterize each binding site individually, EPR-silent Cd2+ ions were used to saturate the other binding sites. This cadmium-induced EPR silencing showed that the Mn2+ binding sites possess different affinities. In addition, these binding sites could be assigned to three different types, including innersphere, outersphere, and a Mn2+ dimer. Based on simulations, the Mn2+-Mn2+ distance within the dimer was found to be ∼6 Å, which is in good agreement with crystallographic data. The EPR-spectroscopic characterization reveals no structural changes upon addition of a Diels-Alder product, supporting the concept of a preorganized catalytic pocket in the Diels-Alder ribozyme and the structural role of these ions. PMID:19404418

Preliminary investigation of a sealed, remotely activated silver-zinc battery

NASA Technical Reports Server (NTRS)

Wheat, C. G.

1977-01-01

Methods necessary to provide a remotely activated, silver zinc battery capable of an extended activated stand while in a sealed condition were investigated. These requirements were to be accomplished in a battery package demonstrating an energy density of at least 35 watt hours per pound. Several methods of gas suppression were considered in view of the primary nature of this unit and utilized the electroplated dendritic zinc electrode. Amalgamation of the electrode provided the greatest suppression of gas at the zinc electrode. The approach to extending the activated stand capability of the remotely activated battery was through evaluation of three basic methods of remote, multi-cell activation; 1) the electrolyte manifold, 2) the gas manifold and 3) the individual cell. All three methods of activation can be incorporated into units which will meet the minimum energy density requirement.

The significance of the source of zinc and its anti-VSC effect.

PubMed

Rölla, G; Jonski, G; Young, A

2002-06-01

The anti-VSC (volatile sulphur compounds) effect of zinc is known to be associated with free zinc ions. To examine whether zinc salts with low stability constants were more suitable as sources of zinc in zinc lozenges than zinc salts with high stability constants. The former provide free zinc ions upon dissolution in water, whereas the latter provide few such ions. Identical lozenges were produced which contained either zinc acetate, zinc gluconate (low stability constants), zinc citrate or amino-acid chelated zinc (extremely high stability constants). All the lozenges contained 0.1 per cent of zinc. A test panel of 10 volunteers used the different lozenges randomly. VSC were measured by GC. The lozenge with the highest stability constant was as effective as those with very low stability constants. The anti-VSC effect was thus not related to this constant. These findings may be explained by the possibility that alternative ligands with stronger affinity for zinc than the original ligands in the lozenges may be present in the oral cavity. An in vitro experiment indicated that the sulphide ion (S2-) may be such a ligand.

Comparative genomics of bacterial zinc regulons: enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins.

PubMed

Panina, Ekaterina M; Mironov, Andrey A; Gelfand, Mikhail S

2003-08-19

Zinc is an important component of many proteins, but in large concentrations it is poisonous to the cell. Thus its transport is regulated by zinc repressors ZUR of proteobacteria and Gram-positive bacteria from the Bacillus group and AdcR of bacteria from the Streptococcus group. Comparative computational analysis allowed us to identify binding signals of ZUR repressors GAAATGTTATANTATAACATTTC for gamma-proteobacteria, GTAATGTAATAACATTAC for the Agrobacterium group, GATATGTTATAACATATC for the Rhododoccus group, TAAATCGTAATNATTACGATTTA for Gram-positive bacteria, and TTAACYRGTTAA of the streptococcal AdcR repressor. In addition to known transporters and their paralogs, zinc regulons were predicted to contain a candidate component of the ATP binding cassette, zinT (b1995 in Escherichia coli and yrpE in Bacillus subtilis). Candidate AdcR-binding sites were identified upstream of genes encoding pneumococcal histidine triad (PHT) proteins from a number of pathogenic streptococci. Protein functional analysis of this family suggests that PHT proteins are involved in the invasion process. Finally, repression by zinc was predicted for genes encoding a variety of paralogs of ribosomal proteins. The original copies of all these proteins contain zinc-ribbon motifs and thus likely bind zinc, whereas these motifs are destroyed in zinc-regulated paralogs. We suggest that the induction of these paralogs in conditions of zinc starvation leads to their incorporation in a fraction of ribosomes instead of the original ribosomal proteins; the latter are then degraded with subsequent release of some zinc for the utilization by other proteins. Thus we predict a mechanism for maintaining zinc availability for essential enzymes.

The active site structure of tetanus neurotoxin resolved by multiple scattering analysis in X-Ray absorption spectroscopy.

PubMed Central

Meneghini, C; Morante, S

1998-01-01

A detailed study of the x-ray absorption spectrum of tetanus neurotoxin in the K-edge EXAFS region of the zinc absorber is presented that allows the complete identification of the amino acid residues coordinated to the zinc active site. A very satisfactory interpretation of the experimental data can be given if multiple scattering contributions are included in the analysis. Comparing the absorption spectrum of tetanus neurotoxin to that of two other structurally similar zinc-endopeptidases, thermolysin and astacin, in which the zinc coordination mode is known from crystallographic data, we conclude that in tetanus neurotoxin, besides a water molecule, zinc is coordinated to two histidines and a tyrosine. PMID:9746536

Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Derebe, Mehabaw G.; Sauer, David B.; Zeng, Weizhong

2015-11-30

Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K{sup +} channel selectivity filters. Combined with single channel electrophysiology, we show that only themore » channel with four ion binding sites is K{sup +} selective, whereas those with two or three are nonselective and permeate Na{sup +} and K{sup +} equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K{sup +} channels is essential for highly selective and efficient permeation of K{sup +} ions.« less

Revisiting and re-engineering the classical zinc finger peptide: consensus peptide-1 (CP-1).

PubMed

Besold, Angelique N; Widger, Leland R; Namuswe, Frances; Michalek, Jamie L; Michel, Sarah L J; Goldberg, David P

2016-04-01

Zinc plays key structural and catalytic roles in biology. Structural zinc sites are often referred to as zinc finger (ZF) sites, and the classical ZF contains a Cys2His2 motif that is involved in coordinating Zn(II). An optimized Cys2His2 ZF, named consensus peptide 1 (CP-1), was identified more than 20 years ago using a limited set of sequenced proteins. We have reexamined the CP-1 sequence, using our current, much larger database of sequenced proteins that have been identified from high-throughput sequencing methods, and found the sequence to be largely unchanged. The CCHH ligand set of CP-1 was then altered to a CAHH motif to impart hydrolytic activity. This ligand set mimics the His2Cys ligand set of peptide deformylase (PDF), a hydrolytically active M(II)-centered (M = Zn or Fe) protein. The resultant peptide [CP-1(CAHH)] was evaluated for its ability to coordinate Zn(II) and Co(II) ions, adopt secondary structure, and promote hydrolysis. CP-1(CAHH) was found to coordinate Co(II) and Zn(II) and a pentacoordinate geometry for Co(II)-CP-1(CAHH) was implicated from UV-vis data. This suggests a His2Cys(H2O)2 environment at the metal center. The Zn(II)-bound CP-1(CAHH) was shown to adopt partial secondary structure by 1-D (1)H NMR spectroscopy. Both Zn(II)-CP-1(CAHH) and Co(II)-CP-1(CAHH) show good hydrolytic activity toward the test substrate 4-nitrophenyl acetate, exhibiting faster rates than most active synthetic Zn(II) complexes.

Differential regulation of ASICs and TRPV1 by zinc in rat bronchopulmonary sensory neurons.

PubMed

Vysotskaya, Zhanna V; Moss, Charles R; Gu, Qihai

2014-12-01

Zinc has been known to act as a signaling molecule that regulates a variety of neuronal functions. In this study, we aimed to study the effect of zinc on two populations of acid-sensitive ion channels, acid-sensing ion channels (ASICs), and transient receptor potential vanilloid receptor-1 (TRPV1), in vagal bronchopulmonary sensory neurons. Rat vagal sensory neurons innervating lungs and airways were retrogradely labeled with a fluorescent tracer. Whole-cell perforated patch-clamp recordings were carried out in primarily cultured bronchopulmonary sensory neurons. The acid-evoked ASIC and TRPV1 currents were measured and compared between before and after the zinc pretreatment. ASIC currents were induced by a pH drop from 7.4 to 6.8 or 6.5 in the presence of capsazepine (10 µM), a specific TRPV1 antagonist. Pretreatment with zinc (50 or 300 µM, 2 min) displayed different effects on the two distinct phenotypes of ASIC currents: a marked potentiation on ASIC channels with fast kinetics of activation and inactivation or no significant effect on ASIC currents with slow activation and inactivation. On the other hand, pretreatment with zinc significantly inhibited the acid (pH 5.5 or 5.3)-induced TRPV1 currents. The inhibition was abolished by intracellular chelation of zinc by TPEN (25 µM), indicating that intracellular accumulation of zinc was likely required for its inhibitory effect on TRPV1 channels. Our study showed that zinc differentially regulates the activities of ASICs and TRPV1 channels in rat vagal bronchopulmonary sensory neurons.

Structure of the endonuclease IV homologue from Thermotoga maritima in the presence of active-site divalent metal ions

PubMed Central

Tomanicek, Stephen J.; Hughes, Ronny C.; Ng, Joseph D.; Coates, Leighton

2010-01-01

The most frequent lesion in DNA is at apurinic/apyrimidinic (AP) sites resulting from DNA-base losses. These AP-site lesions can stall DNA replication and lead to genome instability if left unrepaired. The AP endonucleases are an important class of enzymes that are involved in the repair of AP-site intermediates during damage-general DNA base-excision repair pathways. These enzymes hydrolytically cleave the 5′-phosphodiester bond at an AP site to generate a free 3′-­hydroxyl group and a 5′-terminal sugar phosphate using their AP nuclease activity. Specifically, Thermotoga maritima endonuclease IV is a member of the second conserved AP endonuclease family that includes Escherichia coli endonuclease IV, which is the archetype of the AP endonuclease superfamily. In order to more fully characterize the AP endonuclease family of enzymes, two X-­ray crystal structures of the T. maritima endonuclease IV homologue were determined in the presence of divalent metal ions bound in the active-site region. These structures of the T. maritima endonuclease IV homologue further revealed the use of the TIM-barrel fold and the trinuclear metal binding site as important highly conserved structural elements that are involved in DNA-binding and AP-site repair processes in the AP endonuclease superfamily. PMID:20823514

The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.

PubMed

Corbi, N; Libri, V; Fanciulli, M; Tinsley, J M; Davies, K E; Passananti, C

2000-06-01

Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.

Mononuclear zinc(II) complexes of 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols: Synthesis, structural characterization, DNA binding and cheminuclease activities

NASA Astrophysics Data System (ADS)

Ravichandran, J.; Gurumoorthy, P.; Karthick, C.; Kalilur Rahiman, A.

2014-03-01

Four new zinc(II) complexes [Zn(HL1-4)Cl2] (1-4), where HL1-4 = 2-((2-(piperazin-1-yl)ethylimino)methyl)-4-substituted phenols, have been isolated and fully characterized using various spectro-analytical techniques. The X-ray crystal structure of complex 4 shows the distorted trigonal-bipyramidal coordination geometry around zinc(II) ion. The crystal packing is stabilized by intermolecular NH⋯O hydrogen bonding interaction. The complexes display no d-d electronic band in the visible region due to d10 electronic configuration of zinc(II) ion. The electrochemical properties of the synthesized ligands and their complexes exhibit similar voltammogram at reduction potential due to electrochemically innocent Zn(II) ion, which evidenced that the electron transfer is due to the nature of the ligand. Binding interaction of complexes with calf thymus DNA was studied by UV-Vis absorption titration, viscometric titration and cyclic voltammetry. All complexes bind with CT DNA by intercalation, giving the binding affinity in the order of 2 > 1 ≫ 3 > 4. The prominent cheminuclease activity of complexes on plasmid DNA (pBR322 DNA) was observed in the absence and presence of H2O2. Oxidative pathway reveals that the underlying mechanism involves hydroxyl radical.

Negative modulation of presynaptic activity by zinc released from Schaffer collaterals.

PubMed

Takeda, Atsushi; Fuke, Sayuri; Tsutsumi, Wataru; Oku, Naoto

2007-12-01

The role of zinc in excitation of Schaffer collateral-CA1 pyramidal cell synapses is poorly understood. Schaffer collaterals stained with ZnAF-2 or ZnAF-2DA, a membrane-impermeable or a membrane-permeable zinc indicator, respectively, were treated by tetanic stimulation (200 Hz, 1 sec). Extracellular and intracellular ZnAF-2 signals were increased in the stratum radiatum of the CA1, in which Schaffer collateral synapses exist. Both the increases were completely blocked in the presence of 1 mM CaEDAT, a membrane-impermeable zinc chelator, suggesting that 1 mM CaEDTA is effective for chelating zinc released from Schaffer collaterals. The role of Schaffer collateral zinc in presynaptic activity was examined by using FM4-64, a fluorescent indicator for vesicular exocytosis. The decrease in FM4-64 signal during tetanic stimulation (10 Hz, 180 sec) was enhanced in Schaffer collaterals in the presence of 1 mM CaEDTA but suppressed in the presence of 5 microM ZnC1(2), suggesting that zinc released from Schaffer collaterals suppresses presynaptic activity during tetanic stimulation. When Schaffer collateral synapses stained with calcium orange AM, a membrane-permeable calcium indicator, were regionally stimulated with 1 mM glutamate, calcium orange signal was increased in the CA1 pyramidal cell layer. This increase was enhanced in the presence of CaEDTA and attenuated in the presence of zinc. These results suggest that zinc attenuates excitation of Schaffer collateral synapses elicited with glutamate via suppression of presynaptic activity. (c) 2007 Wiley-Liss, Inc.

Influence of zinc on the calcium carbonate biomineralization of Halomonas halophila

PubMed Central

2012-01-01

Background The salt tolerance of halophilic bacteria make them promising candidates for technical applications, like isolation of salt tolerant enzymes or remediation of contaminated saline soils and waters. Furthermore, some halophilic bacteria synthesize inorganic solids resulting in organic–inorganic hybrids. This process is known as biomineralization, which is induced and/or controlled by the organism. The adaption of the soft and eco-friendly reaction conditions of this formation process to technical syntheses of inorganic nano materials is desirable. In addition, environmental contaminations can be entrapped in biomineralization products which facilitate the subsequent removal from waste waters. The moderately halophilic bacteria Halomonas halophila mineralize calcium carbonate in the calcite polymorph. The biomineralization process was investigated in the presence of zinc ions as a toxic model contaminant. In particular, the time course of the mineralization process and the influence of zinc on the mineralized inorganic materials have been focused in this study. Results H. halophila can adapt to zinc contaminated medium, maintaining the ability for biomineralization of calcium carbonate. Adapted cultures show only a low influence of zinc on the growth rate. In the time course of cultivation, zinc ions accumulated on the bacterial surface while the medium depleted in the zinc contamination. Intracellular zinc concentrations were below the detection limit, suggesting that zinc was mainly bound extracellular. Zinc ions influence the biomineralization process. In the presence of zinc, the polymorphs monohydrocalcite and vaterite were mineralized, instead of calcite which is synthesized in zinc-free medium. Conclusions We have demonstrated that the bacterial mineralization process can be influenced by zinc ions resulting in the modification of the synthesized calcium carbonate polymorph. In addition, the shape of the mineralized inorganic material is chancing

Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus.

PubMed

Foster, Meika; Samman, Samir

2010-11-15

Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3′-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

Mercury removal from aqueous solutions by zinc cementation.

PubMed

Ku, Young; Wu, Ming-Huan; Shen, Yung-Shen

2002-01-01

The main purpose of this research is to study the addition effect of the surfactant and other operating factors on the treatment of wastewater containing mercury ions in aqueous solution by cementation with sacrificing metal, zinc. The removal of mercury ions from aqueous solutions by cementation of zinc powder was found to be a function of solution pH and temperature, amount of zinc, concentration of mercury ion, contact time and the addition of several organic surfactants. Cementation of mercury was shown to be a feasible process to achieve a very high degree of mercury removal over a broad operational range within a fairly reasonable contact time. The reaction rate is approximately first order with respect to the concentration of mercury ion in aqueous solution. Among the surfactants used in this study, only the presence of SDS, an anionic surfactant, slightly enhanced the cementation rate of mercury. The presence of CTAB and Triton-X100 retarded the cementation of mercury by zinc.

Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Xi; Zhou, Xixi; Du, Libo

2014-01-15

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects ofmore » arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of

Endogenous Zinc in Neurological Diseases

PubMed Central

2005-01-01

The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

Zinc(II) complexes with heterocyclic ether, acid and amide. Crystal structure, spectral, thermal and antibacterial activity studies

NASA Astrophysics Data System (ADS)

Jabłońska-Wawrzycka, Agnieszka; Rogala, Patrycja; Czerwonka, Grzegorz; Hodorowicz, Maciej; Stadnicka, Katarzyna

2016-02-01

The reaction of zinc salts with heterocyclic ether (1-ethoxymethyl-2-methylimidazole (1-ExMe-2-MeIm)), acid (pyridine-2,3-dicarboxylic acid (2,3-pydcH2)) and amide (3,5-dimethylpyrazole-1-carboxamide (3,5-DMePzCONH2)) yielded three new zinc complexes formulated as [Zn(1-ExMe-2-MeIm)2Cl2] 1, fac-[Zn(H2O)6][Zn(2,3-pydcH)3]22 and [Zn(3,5-DMePz)2(NCO)2] 3. Complexes of 1 and 3 are four-coordinated with a tetrahedron as coordination polyhedron. However, compound 2 forms an octahedral cation-anion complex. The complex 3 was prepared by eliminating of the carboxamide group from the ligand and then the 3,5-dimethylpyrazole (3,5-DMePz) and isocyanates formed were employed as new ligands. The IR and X-ray studies have confirmed a bidentate fashion of coordination of the 2,3-pydcH and monodentate fashion of coordination of the 1-ExMe-2-MeIm and 3,5-DMePz to the Zn(II) ions. The crystal packing of Zn(II) complexes are stabilized by intermolecular classical hydrogen bonds of O-H⋯O and N-H⋯O types. The most interesting feature of the supramolecular architecture of complexes is the existence of C-H⋯O, C-H⋯Cl and C-H⋯π interactions and π⋯π stacking, which also contributes to structural stabilisation. The correlation between crystal structure and thermal stability of zinc complexes is observed. In all compounds the fragments of ligands donor-atom containing go in the last steps. Additionally, antimicrobial activities of compounds were carried out against certain Gram-positive and Gram-negative bacteria and counts of CFU (colony forming units) were also determined. The achieved results confirmed a significant antibacterial activity of some tested zinc complexes. On the basis of the Δ log CFU values the antibacterial activity of zinc complexes follows the order: 3 > 2 > 1. Influence a number of N-donor atoms in zinc environment on antibacterial activity is also observed.

Batch sorption dynamics and equilibrium for the removal of lead ions from aqueous phase using activated carbon developed from coffee residue activated with zinc chloride.

PubMed

Boudrahem, F; Aissani-Benissad, F; Aït-Amar, H

2009-07-01

Lignocellulosic materials are good precursors for the production of activated carbon. In this work, coffee residue has been used as raw material in the preparation of powder activated carbon by the method of chemical activation with zinc chloride for the sorption of Pb(II) from dilute aqueous solutions. The influence of impregnation ratio (ZnCl2/coffee residue) on the physical and chemical properties of the prepared carbons was studied in order to optimize this parameter. The optimum experimental condition for preparing predominantly microporous activated carbons with high pore surface area (890 m2/g) and micropore volume (0.772 cm3/g) is an impregnation ratio of 100%. The developed activated carbon shows substantial capability to sorb lead(II) ions from aqueous solutions and for relative impregnation ratios of 75 and 100%, the maximum uptake is practically the same. Thus, 75% represents the optimal impregnation ratio. Batch experiments were conducted to study the effects of the main parameters such as contact time, initial concentration of Pb(II), solution pH, ionic strength and temperature. The maximum uptake of lead(II) at 25 degrees C was about 63 mg/g of adsorbent at pH 5.8, initial Pb(II) concentration of 10 mg/L, agitation speed of 200 rpm and ionic strength of 0.005 M. The kinetic data were fitted to the models of pseudo-first order and pseudo-second order, and follow closely the pseudo-second order model. Equilibrium sorption isotherms of Pb(II) were analyzed by the Langmuir, Freundlich and Temkin isotherm models. The Freundlich model gives a better fit than the others. Results from this study suggest that activated carbon produced from coffee residue is an effective adsorbent for the removal of lead from aqueous solutions and that ZnCl2 is a suitable activating agent for the preparation of high-porosity carbons.

Zinc naphthalenedicarboxylate coordination complex: A promising anode material for lithium and sodium-ion batteries with good cycling stability.

PubMed

Fei, Hailong; Feng, Wenjing; Xu, Tan

2017-02-15

It is important to discover new, cheap and environmental friendly electrode materials with high capacity and good cycling stability for lithium and sodium-ion batteries. Zinc 1,4-naphthalenedicarboxylate was firstly found to be stable anode materials for lithium and sodium-ion batteries. The discharge capacity can be up to 468.9mAhg -1 after 100 cycles at a current density of 100mAg -1 for lithium-ion batteries, while the second discharge capacity of 320.7mAhg -1 was achieved as anode materials for sodium-ion batteries. A possible electrochemical reaction mechanism was discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Thiol versus hydroxamate as zinc binding group in HDAC inhibition: An ab initio QM/MM molecular dynamics study.

PubMed

Gong, Wenjing; Wu, Ruibo; Zhang, Yingkai

2015-11-15

Zinc-dependent histone deacetylases (HDACs) play a critical role in transcriptional repression and gene silencing, and are among the most attractive targets for the development of new therapeutics against cancer and various other diseases. Two HDAC inhibitors have been approved by FDA as anti-cancer drugs: one is SAHA whose hydroxamate is directly bound to zinc, the other is FK228 whose active form may use thiol as the zinc binding group. In spite of extensive studies, it remains to be ambiguous regarding how thiol and hydroxamate are bound to the zinc active site of HDACs. In this work, our computational approaches center on Born-Oppenheimer ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics with umbrella sampling, which allow for modeling of the zinc active site with reasonable accuracy while properly including dynamics and effects of protein environment. Meanwhile, an improved short-long effective function (SLEF2) to describe non-bonded interactions between zinc and other atoms has been employed in initial MM equilibrations. Our ab initio QM/MM MD simulations have confirmed that hydroxamate is neutral when it is bound to HDAC8, and found that thiol is deprotonated when directly bound to zinc in the HDAC active site. By comparing thiol and hydroxamate, our results elucidated the differences in their binding environment in the HDAC active sites, and emphasized the importance of the linker design to achieve more specific binding toward class IIa HDACs. © 2015 Wiley Periodicals, Inc.

Thiol Versus Hydroxamate as Zinc Binding Group In HDAC Inhibition: An Ab Initio QM/MM Molecular Dynamics Study

PubMed Central

Gong, Wenjing; Wu, Ruibo; Zhang, Yingkai

2015-01-01

Zinc-dependent histone deacetylases (HDACs) play a critical role in transcriptional repression and gene silencing, and are among the most attractive targets for the development of new therapeutics against cancer and various other diseases. Two HDAC inhibitors have been approved by FDA as anti-cancer drugs: one is SAHA whose hydroxamate is directly bound to zinc, the other is FK228 whose active form may use thiol as the zinc binding group. In spite of extensive studies, it remains to be ambiguous regarding how thiol and hydroxamate are bound to the zinc active site of HDACs. In this work, our computational approaches center on Born-Oppenheimer ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics with umbrella sampling, which allow for modeling of the zinc active site with reasonable accuracy while properly including dynamics and effects of protein environment. Meanwhile, an improved short-long effective function (SLEF2) to describe non-bonded interactions between zinc and other atoms has been employed in initial MM equilibrations. Our ab initio QM/MM MD simulations have confirmed that hydroxamate is neutral when it is bound to HDAC8, and found that thiol is deprotonated when directly bound to zinc in the HDAC active site. By comparing thiol and hydroxamate, our results elucidated the differences in their binding environment in the HDAC active sites, and emphasized the importance of the linker design to achieve more specific binding towards class IIa HDACs. PMID:26452222

Zinc ion enhances GABA tea-mediated oxidative DNA damage.

PubMed

Chuang, Show-Mei; Wang, Hsueh-Fang; Hsiao, Ching-Chuan; Cherng, Shur-Hueih

2012-02-15

GABA tea is a tea product that contains a high level of γ-aminobutyric acid (GABA). Previous study has demonstrated a synergistic effect of GABA tea and copper ions on DNA breakage. This study further explored whether zinc (Zn), a nonredox metal, modulated DNA cleavage induced by GABA tea extract. In a cell-free system, Zn(2+) significantly enhanced GABA tea extract and (-)-epigallocatechin-3-gallate (EGCG)- or H(2)O(2)-induced DNA damage at 24 h of incubation. Additionally, low dosages of GABA tea extract (1-10 μg/mL) possessed pro-oxidant activity to increase H(2)O(2)/Zn(2+)-induced DNA cleavage in a dose-dependent profile. By use of various reactive oxygen scavengers, it was observed that glutathione, catalase, and potassium iodide effectively inhibited DNA degradation caused by the GABA tea extract/H(2)O(2)/Zn(2+) system. Moreover, the data showed that the GABA tea extract itself (0.5-5 mg/mL) could induce DNA cleavage in a long-term exposure (48 h). EGCG, but not the GABA tea extract, enhanced H(2)O(2)-induced DNA cleavage. In contrast, GABA decreased H(2)O(2)- and EGCG-induced DNA cleavage, suggesting that GABA might contribute the major effect on the antioxidant activity of GABA tea extract. Furthermore, a comet assay revealed that GABA tea extract (0.25 mg/mL) and GABA had antioxidant activity on H(2)O(2)-induced DNA breakage in human peripheral lymphocytes. Taken together, these findings indicate that GABA tea has the potential of both pro-oxidant and antioxidant. It is proposed that a balance between EGCG-induced pro-oxidation and GABA-mediated antioxidation may occur in a complex mixture of GABA tea extract.

Dynamic ion-ion and water-ion interactions in ion channels.

PubMed Central

Wu, J V

1992-01-01

The dynamic interactions among ions and water molecules in ion channels are treated based on an assumption that ions at binding sites can be knocked off by both transient entering ions and local water molecules. The theory, when applied to a single-site model K+ channel, provides solutions for super- and subsaturations, flux-ratio exponent (n') greater than 1, osmotic streaming current, activity-dependent reversal potentials, and anomalous mole-fraction behavior. The analysis predicts that: (a) the saturation may but, in general, does not follow the Michaelis-Menten relation; (b) streaming current results from imbalanced water-ion knock-off interactions; (c) n' greater than 1 even for single-site channels, but it is unlikely to exceed 1.4 unless the pore is occupied by one or more ion(s); (d) in the calculation involving two permeant ion species with similar radii, the heavier ions show higher affinity; the ion-ion knock-off dissociation from the site is more effective when two interacting ions are identical. Therefore, the "multi-ion behaviors" found in most ion channels are the consequences of dynamic ion-ion and water-ion interactions. The presence of these interactions does not require two or more binding sites in channels. PMID:1376158

Zinc transporters and dysregulated channels in cancers

PubMed Central

Pan, Zui; Choi, Sangyong; Ouadid-Ahidouch, Halima; Yang, Jin-Ming; Beattie, John H.; Korichneva, Irina

2016-01-01

As a nutritionally essential metal ion, zinc (Zn) not only constitutes a structural element for more than 3000 proteins but also plays important regulatory functions in cellular signal transduction. Zn homeostasis is tightly controlled by regulating the flux of Zn across cell membranes through specific transporters, i.e. ZnT and ZIP family proteins. Zn deficiency and malfunction of Zn transporters have been associated with many chronic diseases including cancer. However, the mechanisms underlying Zn regulatory functions in cellular signaling and their impact on the pathogenesis and progression of cancers remain largely unknown. In addition to these acknowledged multifunctions, Zn modulates a wide range of ion channels that in turn may also play an important role in cancer biology. The goal of this review is to propose how zinc deficiency, through modified Zn homeostasis, transporter activity and the putative regulatory function of Zn can influence ion channel activity, and thereby contribute to carcinogenesis and tumorigenesis. This review intends to stimulate interest in, and support for research into the understanding of Zn-modulated channels in cancers, and to search for novel biomarkers facilitating effective clinical stratification of high risk cancer patients as well as improved prevention and therapy in this emerging field. PMID:27814637

Entrapment of Carbon Dioxide in the Active Site of Carbonic Anhydrase II*♦

PubMed Central

Domsic, John F.; Avvaru, Balendu Sankara; Kim, Chae Un; Gruner, Sol M.; Agbandje-McKenna, Mavis; Silverman, David N.; McKenna, Robert

2008-01-01

The visualization at near atomic resolution of transient substrates in the active site of enzymes is fundamental to fully understanding their mechanism of action. Here we show the application of using CO2-pressurized, cryo-cooled crystals to capture the first step of CO2 hydration catalyzed by the zinc-metalloenzyme human carbonic anhydrase II, the binding of substrate CO2, for both the holo and the apo (without zinc) enzyme to 1.1Å resolution. Until now, the feasibility of such a study was thought to be technically too challenging because of the low solubility of CO2 and the fast turnover to bicarbonate by the enzyme (Liang, J. Y., and Lipscomb, W. N. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 3675–3679). These structures provide insight into the long hypothesized binding of CO2 in a hydrophobic pocket at the active site and demonstrate that the zinc does not play a critical role in the binding or orientation of CO2. This method may also have a much broader implication for the study of other enzymes for which CO2 is a substrate or product and for the capturing of transient substrates and revealing hydrophobic pockets in proteins. PMID:18768466

On the formation of nanocrystalline active zinc oxide from zinc hydroxide carbonate

NASA Astrophysics Data System (ADS)

Moezzi, Amir; Cortie, Michael; Dowd, Annette; McDonagh, Andrew

2014-04-01

The decomposition of zinc hydroxide carbonate, Zn5(CO3)2(OH)6 (ZHC), into the high surface area form of ZnO known as "active zinc oxide" is examined. In particular, the nucleation and evolution of the ZnO nanocrystals is of interest as the size of these particles controls the activity of the product. The decomposition process was studied using X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy and BET surface area measurements. At about 240 °C ZHC decomposes to porous ZnO in a single step. The product material has a specific surface area in the range of 47-65 m2 g-1 and initially has a crystallite size that is of the order of 10 nm. A further increase in temperature, however, causes the particles to coarsen to over 25 nm in diameter. In principle, the coarsening phenomenon may be interrupted to control the particle size.

5-Arylvinyl-2,2′-bipyridyls: Bright “push–pull” dyes as components in fluorescent indicators for zinc ions

PubMed Central

Zhu, Lei; Younes, Ali H.; Yuan, Zhao; Clark, Ronald J.

2015-01-01

This article reviews the zinc(II)-dependent photophysical properties of arylvinylbipyridines (AVBs), a class of fluoroionophores in which 2,2′-bipyridyl and an aryl moiety are electronically conjugated. Zinc(II) binding of an AVB may lead to an emission bathochromic shift of the fluoroionophore without diminishing its fluorescence quantum yield. This observation can be explained using the excited state model of electron donor–π bridge–electron acceptor “push–pull” fluorophores, in which the bipy moiety acts as an electron acceptor, and zinc(II)-coordination strengthens its electron affinity. The spectral sensitivity of bipy-containing fluoroionophores, such as AVBs, to zinc(II) can be exploited to prepare fluorescent indicators for this ion. In several cases, AVB moieties are incorporated in fluorescent heteroditopic ligands, so that the variation of zinc(II) concentration over a relatively large range can be correlated to fluorescence changes in either intensity or color. AVB fluoroionophores are also used to introduce an intramolecular Förster resonance energy transfer (FRET) strategy for creating zinc(II) indicators with high photostability and a narrow emission band, two desired characteristics of dyes used in fluorescence microscopy. PMID:26190906

Expression of zinc transporter ZnT7 in mouse superior cervical ganglion

USDA-ARS?s Scientific Manuscript database

The superior cervical ganglion (SCG) neurons contain a considerable amount of zinc ions, but little is known about zinc homeostasis in the SCG. It is known that zinc transporter 7 (ZnT7, Slc30a7), a member of the Slc30 ZnT family, is involved in mobilizing zinc ions from the cytoplasm into the Golgi...

Effects of zinc and female aging on nymphal life history in a grasshopper from polluted sites.

PubMed

Augustyniak, Maria; Babczyńska, Agnieszka; Kozłowski, Michał; Sawczyn, Tomasz; Augustyniak, Michał

2008-01-01

Insect reproduction is influenced by various factors, including food quality and quantity, temperature, population density and female age. Contamination, including heavy metals, may disturb reproductive processes. The aim of this work was to assess interactions between effects of aging in female Chorthippus brunneus and environmental pollution on their reproduction measured in number of laid eggs. We also compared basic developmental parameters (number of hatchlings, body mass, embryonic developmental rate) in grasshopper nymphs additionally exposed to zinc during diapause. Aging grasshoppers from heavily polluted areas (Olkusz and Szopienice) lay significantly fewer eggs than insects from the reference site (Pilica). Zinc application caused the decrease in hatching success and duration of embryogenesis in insects from each site. This suggests a cumulative effect of female age, pollutants and additional stressing factors. The intensity of this process differed between populations. In insects from the reference site, it was shown in a moderate degree. In insects from Szopienice, an additional stressor exerted a weaker effect than in insects from Pilica. In grasshoppers from Olkusz, we found the strongest decrease of hatching percentage and increase in duration of embryogenesis after zinc intoxication. This may indicate that the population from Olkusz exists at the limit of its energetic abilities.

Catalytic zinc site and mechanism of the metalloenzyme PR-AMP cyclohydrolase.

PubMed

D'Ordine, Robert L; Linger, Rebecca S; Thai, Carolyn J; Davisson, V Jo

2012-07-24

three conserved cysteine residues. The C93 reactivity is modulated by the presence of the Zn(2+) and Mg(2+) and substantiates the role of this residue as a metal ligand. In addition, Mg(2+) ligand binding site(s) indicated by the structural analysis were probed by site-directed mutagenesis of three key aspartate residues flanking the conserved C93 which were shown to have a functional impact on catalysis, cysteine activation, and metal (zinc) binding capacity. The unique amino acid sequence, the dynamic properties of the cysteine ligands involved in Zn(2+) coordination, and the requirement for a second metal (Mg(2+)) are discussed in the context of their roles in catalysis. The results are consistent with a Zn(2+)-mediated activation of H(2)O mechanism involving histidine as a general base that has features similar to but distinct from those of previously characterized purine and pyrimidine deaminases.

Zinc

MedlinePlus

... Using toothpastes containing zinc, with or without an antibacterial agent, appears to prevent plaque and gingivitis. Some ... is some evidence that zinc has some antiviral activity against the herpes virus. Low zinc levels can ...

Role of zinc in chronic gastritis.

PubMed

Marjanović, Ksenija; Dovhanj, Jasna; Kljaić, Ksenija; Sakić, Katarina; Kondza, Goran; Tadzić, Refmir; Vcev, Aleksandar

2010-06-01

Oxidative stress occurs in inflammation of gastric mucosa. The role of zinc in modulating oxidative stress has recently been recognized. Zn deficiency results in an increased sensitivity to oxidative stress and have a higher risk of musoca damage in inflammation. The aim of this study was to determine wheather chronic inflammation affects on the concentration of Zn2+ ions in gastric mucosa of patients with chronic gastritis. Forthy-three patients with chronic gastitis were enrolled. Patients were endoscoped. Histology and scoring of gastritis was performed following the guidelines of the updated Sydney system. Endoscopic finding of mucosa were scored according to a Lanza scoring system. The diagnosis of Helicobacter pylori (H. pylori) infection, histopathologic changes, intensity of inflammation and zinc concentration were determined from biopsies of gastric mucosa. The atomic absorption spectrophotometer was used to determine tissue concentrations of zinc. Twenty of 43 patients with chronic gastritis were uninfected by H. pylori. There was no statistically significant difference in tissue concentrations of zinc between H. pylori-positive and H. pylori-negative patients. From those infected patients 53.3% had chronic active gastritis. There was no statistically significant difference in tissue concentrations of zinc between patients with chronic active gastritis and patients with chronic inactive gastritis (p = 0.966). Zn in antrum showed positive correlation with density of H. pylori in antrum (Spearman' rho = 0.481, p = 0.020), negative correlation with density of H. pylori in corpus (Spearman' rho = -0.492, p = 0.017) and with zinc in corpus (Spearman' rho = 0.631, p =0.001). Tissue concentration of zinc was not affected by chronic inflammation of gastric mucosa in patients with chronic gastritis.

Influence of triethyl phosphate on phosphatase activity in shooting range soil: Isolation of a zinc-resistant bacterium with an acid phosphatase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Story, Sandra; Brigmon, Robin L.

Phosphatase-mediated hydrolysis of organic phosphate may be a viable means of stabilizing heavy metals via precipitation as a metal phosphate in bioremediation applications. We investigated the effect of triethyl phosphate (TEP) on soil microbial-phosphatase activity in a heavy-metal contaminated soil. Gaseous TEP has been used at subsurface sites for bioremediation of organic contaminants but not applied in heavy-metal contaminated areas. Little is known about how TEP affects microbial activity in soils and it is postulated that TEP can serve as a phosphate source in nutrient-poor groundwater and soil/sediments. Over a 3-week period, TEP amendment to microcosms containing heavy-metal contaminated soilmore » resulted in increased activity of soil acid-phosphatase and repression of alkaline phosphatase, indicating a stimulatory effect on the microbial population. A soil-free enrichment of microorganisms adapted to heavy-metal and acidic conditions was derived from the TEP-amended soil microcosms using TEP as the sole phosphate source and the selected microbial consortium maintained a high acid-phosphatase activity with repression of alkaline phosphatase. Addition of 5 mM zinc to soil-free microcosms had little effect on acid phosphatase but inhibited alkaline phosphatase. One bacterial member from the consortium, identified as Burkholderia cepacia sp., expressed an acid-phosphatase activity uninhibited by high concentrations of zinc and produced a soluble, indigo pigment under phosphate limitation. The pigment was produced in a phosphate-free medium and was not produced in the presence of TEP or phosphate ion, indicative of purple acid-phosphatase types that are pressed by bioavailable phosphate. Finally, these results demonstrate that TEP amendment was bioavailable and increased overall phosphatase activity in both soil and soil-free microcosms supporting the possibility of positive outcomes in bioremediation applications.« less

Influence of triethyl phosphate on phosphatase activity in shooting range soil: Isolation of a zinc-resistant bacterium with an acid phosphatase

DOE PAGES

Story, Sandra; Brigmon, Robin L.

2016-12-19

Phosphatase-mediated hydrolysis of organic phosphate may be a viable means of stabilizing heavy metals via precipitation as a metal phosphate in bioremediation applications. We investigated the effect of triethyl phosphate (TEP) on soil microbial-phosphatase activity in a heavy-metal contaminated soil. Gaseous TEP has been used at subsurface sites for bioremediation of organic contaminants but not applied in heavy-metal contaminated areas. Little is known about how TEP affects microbial activity in soils and it is postulated that TEP can serve as a phosphate source in nutrient-poor groundwater and soil/sediments. Over a 3-week period, TEP amendment to microcosms containing heavy-metal contaminated soilmore » resulted in increased activity of soil acid-phosphatase and repression of alkaline phosphatase, indicating a stimulatory effect on the microbial population. A soil-free enrichment of microorganisms adapted to heavy-metal and acidic conditions was derived from the TEP-amended soil microcosms using TEP as the sole phosphate source and the selected microbial consortium maintained a high acid-phosphatase activity with repression of alkaline phosphatase. Addition of 5 mM zinc to soil-free microcosms had little effect on acid phosphatase but inhibited alkaline phosphatase. One bacterial member from the consortium, identified as Burkholderia cepacia sp., expressed an acid-phosphatase activity uninhibited by high concentrations of zinc and produced a soluble, indigo pigment under phosphate limitation. The pigment was produced in a phosphate-free medium and was not produced in the presence of TEP or phosphate ion, indicative of purple acid-phosphatase types that are pressed by bioavailable phosphate. Finally, these results demonstrate that TEP amendment was bioavailable and increased overall phosphatase activity in both soil and soil-free microcosms supporting the possibility of positive outcomes in bioremediation applications.« less

Influence of triethyl phosphate on phosphatase activity in shooting range soil: Isolation of a zinc-resistant bacterium with an acid phosphatase.

PubMed

Story, Sandra; Brigmon, Robin L

2017-03-01

Phosphatase-mediated hydrolysis of organic phosphate may be a viable means of stabilizing heavy metals via precipitation as a metal phosphate in bioremediation applications. We investigated the effect of triethyl phosphate (TEP) on soil microbial-phosphatase activity in a heavy-metal contaminated soil. Gaseous TEP has been used at subsurface sites for bioremediation of organic contaminants but not applied in heavy-metal contaminated areas. Little is known about how TEP affects microbial activity in soils and it is postulated that TEP can serve as a phosphate source in nutrient-poor groundwater and soil/sediments. Over a 3-week period, TEP amendment to microcosms containing heavy-metal contaminated soil resulted in increased activity of soil acid-phosphatase and repression of alkaline phosphatase, indicating a stimulatory effect on the microbial population. A soil-free enrichment of microorganisms adapted to heavy-metal and acidic conditions was derived from the TEP-amended soil microcosms using TEP as the sole phosphate source and the selected microbial consortium maintained a high acid-phosphatase activity with repression of alkaline phosphatase. Addition of 5mM zinc to soil-free microcosms had little effect on acid phosphatase but inhibited alkaline phosphatase. One bacterial member from the consortium, identified as Burkholderia cepacia sp., expressed an acid-phosphatase activity uninhibited by high concentrations of zinc and produced a soluble, indigo pigment under phosphate limitation. The pigment was produced in a phosphate-free medium and was not produced in the presence of TEP or phosphate ion, indicative of purple acid-phosphatase types that are pressed by bioavailable phosphate. These results demonstrate that TEP amendment was bioavailable and increased overall phosphatase activity in both soil and soil-free microcosms supporting the possibility of positive outcomes in bioremediation applications. Copyright © 2016. Published by Elsevier Inc.

Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.

PubMed

Vannini, Alessandro; Volpari, Cinzia; Filocamo, Gessica; Casavola, Elena Caroli; Brunetti, Mirko; Renzoni, Debora; Chakravarty, Prasun; Paolini, Chantal; De Francesco, Raffaele; Gallinari, Paola; Steinkühler, Christian; Di Marco, Stefania

2004-10-19

Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.

Zinc metal complex as a sensor for simultaneous detection of fluoride and HSO4(-) ions.

PubMed

Singh, Jasminder; Yadav, Manisha; Singh, Ajnesh; Singh, Narinder

2015-07-28

A Schiff base based tripodal receptor was synthesized and complexed with a zinc metal ion (n17) using a very easy single step process. The resulting complex was fully characterized by CHN and single crystal XRD. The real time application of the complex in aqueous media was devised by preparing its organic nanoparticles (ONPs) and their sensor activity was tested with various anions by observing changes in the fluorescence profile of n17. It was observed that ONPs of n17 responded excellently for fluoride and sulfate, producing two different signals, with detection limits of 4.84 × 10(-12) M and 5.67 × 10(-9) M respectively, without having any interference from each other. The real time application of the sensor was also tested using various samples collected from various daily utility items and found to respond exceptionally well.

Evidence That the [beta] Subunit of Chlamydia trachomatis Ribonucleotide Reductase Is Active with the Manganese Ion of Its Manganese(IV)/Iron(III) Cofactor in Site 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dassama, Laura M.K.; Boal, Amie K.; Krebs, Carsten

2014-10-02

The reaction of a class I ribonucleotide reductase (RNR) begins when a cofactor in the {beta} subunit oxidizes a cysteine residue {approx}35 {angstrom} away in the {alpha} subunit, generating a thiyl radical. In the class Ic enzyme from Chlamydia trachomatis (Ct), the cysteine oxidant is the Mn{sup IV} ion of a Mn{sup IV}/Fe{sup III} cluster, which assembles in a reaction between O{sub 2} and the Mn{sup II}/Fe{sup II} complex of {beta}. The heterodinuclear nature of the cofactor raises the question of which site, 1 or 2, contains the Mn{sup IV} ion. Because site 1 is closer to the conserved locationmore » of the cysteine-oxidizing tyrosyl radical of class Ia and Ib RNRs, we suggested that the Mn{sup IV} ion most likely resides in this site (i.e., {sup 1}Mn{sup IV}/{sup 2}Fe{sup III}), but a subsequent computational study favored its occupation of site 2 ({sup 1}Fe{sup III}/{sup 2}Mn{sup IV}). In this work, we have sought to resolve the location of the Mn{sup IV} ion in Ct RNR-{beta} by correlating X-ray crystallographic anomalous scattering intensities with catalytic activity for samples of the protein reconstituted in vitro by two different procedures. In samples containing primarily Mn{sup IV}/Fe{sup III} clusters, Mn preferentially occupies site 1, but some anomalous scattering from site 2 is observed, implying that both {sup 1}Mn{sup II}/{sup 2}Fe{sup II} and {sup 1}Fe{sup II}/{sup 2}Mn{sup II} complexes are competent to react with O{sub 2} to produce the corresponding oxidized states. However, with diminished Mn{sup II} loading in the reconstitution, there is no evidence for Mn occupancy of site 2, and the greater activity of these 'low-Mn' samples on a per-Mn basis implies that the {sup 1}Mn{sup IV}/{sup 2}Fe{sup III}-{beta} is at least the more active of the two oxidized forms and may be the only active form.« less

The zinc dyshomeostasis hypothesis of Alzheimer's disease.

PubMed

Craddock, Travis J A; Tuszynski, Jack A; Chopra, Deepak; Casey, Noel; Goldstein, Lee E; Hameroff, Stuart R; Tanzi, Rudolph E

2012-01-01

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized

Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS

PubMed Central

Shinde, Ranajit Nivrutti; Karthikeyan, Subramanian; Singh, Balvinder

2017-01-01

3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) catalyzes the conversion of D-ribulose 5-phosphate (Ru5P) to L-3,4-dihydroxy-2-butanone-4-phosphate in the presence of Mg2+. Although crystal structures of DHBPS in complex with Ru5P and non-catalytic metal ions have been reported, structure with Ru5P along with Mg2+ is still elusive. Therefore, mechanistic role played by Mg2+ in the structure of DHBPS is poorly understood. In this study, molecular dynamics simulations of DHBPS-Ru5P complex along with Mg2+ have shown entry of Mg2+ from bulk solvent into active site. Presence of Mg2+ in active site has constrained conformations of Ru5P and has reduced flexibility of loop-2. Formation of hydrogen bonds among Thr-108 and residues - Gly-109, Val-110, Ser-111, and Asp-114 are found to be critical for entry of Mg2+ into active site. Subsequent in silico mutations of residues, Thr-108 and Asp-114 have substantiated the importance of these interactions. Loop-4 of one monomer is being proposed to act as a “lid” covering the active site of other monomer. Further, the conserved nature of residues taking part in the transfer of Mg2+ suggests the same mechanism being present in DHBPS of other microorganisms. Thus, this study provides insights into the functioning of DHBPS that can be used for the designing of inhibitors. PMID:28079168

Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS

NASA Astrophysics Data System (ADS)

Shinde, Ranajit Nivrutti; Karthikeyan, Subramanian; Singh, Balvinder

2017-01-01

3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) catalyzes the conversion of D-ribulose 5-phosphate (Ru5P) to L-3,4-dihydroxy-2-butanone-4-phosphate in the presence of Mg2+. Although crystal structures of DHBPS in complex with Ru5P and non-catalytic metal ions have been reported, structure with Ru5P along with Mg2+ is still elusive. Therefore, mechanistic role played by Mg2+ in the structure of DHBPS is poorly understood. In this study, molecular dynamics simulations of DHBPS-Ru5P complex along with Mg2+ have shown entry of Mg2+ from bulk solvent into active site. Presence of Mg2+ in active site has constrained conformations of Ru5P and has reduced flexibility of loop-2. Formation of hydrogen bonds among Thr-108 and residues - Gly-109, Val-110, Ser-111, and Asp-114 are found to be critical for entry of Mg2+ into active site. Subsequent in silico mutations of residues, Thr-108 and Asp-114 have substantiated the importance of these interactions. Loop-4 of one monomer is being proposed to act as a “lid” covering the active site of other monomer. Further, the conserved nature of residues taking part in the transfer of Mg2+ suggests the same mechanism being present in DHBPS of other microorganisms. Thus, this study provides insights into the functioning of DHBPS that can be used for the designing of inhibitors.

[The effect of heavy metal ions and peptide bioregulators on the expression of chromosome fragile sites in the individuals of different age groups and breast cancer patients].

PubMed

Dzhokhadze, T A; Ganozishvili, M N; Lezhava, T A

2008-09-01

Expression rates of chromosome fragile sites in peripheral blood lymphocytes have been studied in clinically healthy individuals of different age groups (20-38 yrs and 75-86 yrs) and breast cancer patients (8 cases). In individuals with a normal check-up of different age groups the heavy metal (nickel, zinc and cobalt) ions were also examined on their influence on the expression of the fragile sites and the peptide bioregulators (Livagen and Epithalon) were tested on their ability to correct the pattern of expression. Short-term lymphocyte cultures were used as tested material. The analysis showed that the chromosomes of people from young and old age groups differ from each other by the expression pattern of fragile sites - the chromosomes of young individuals were found to be more active by spontaneous formation of fragile sites. They were also sensitive to their induction by heavy metals. Both tested bioregulators lessen heavy metals effect that was statistically reliable only for the young people group. As for the patients with breast cancer general elevated fragility of chromosomes and specific distribution of the fragile sites along the chromosomes were revealed.

Zinc phosphate conversion coatings

DOEpatents

Sugama, Toshifumi

1997-01-01

Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate .alpha.-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal.

Using fluorescence measurement of zinc ions liberated from ZnS nanoparticle labels in bioassay for Escherichia coli O157:H7

NASA Astrophysics Data System (ADS)

Cowles, Chad L.; Zhu, Xiaoshan; Pai, Chi-Yun

2011-10-01

In this study, an alternative approach using ZnS nanoparticle biolabels as fluorescence signal transducers is reported for the immunoassay of E. coli O157:H7 in tap water samples. Instead of measuring the fluorescence of ZnS nanoparticles in the assay, the fluorescence signal is generated through the binding of zinc ions released from nanoparticle labels with zinc-ion sensitive fluorescence indicator Fluozin-3. In the assay, ZnS nanoparticles around 50 nm in diameter were synthesized, bioconjugated, and applied for the detection of E. coli O157:H7. The assay shows a detection range over two orders of magnitude and a detection limit around 1000 colony-forming units (cfu) of E. coli O157:H7.

Zinc-Containing Hydroxyapatite Enhances Cold-Light-Activated Tooth Bleaching Treatment In Vitro

PubMed Central

Shi, Xinchang

2017-01-01

Cold-light bleaching treatment has grown to be a popular tooth whitening procedure in recent years, but its side effect of dental enamel demineralization is a widespread problem. The aim of this study was to synthesize zinc-substituted hydroxyapatite as an effective biomaterial to inhibit demineralization or increase remineralization. We synthesized zinc-substituted hydroxyapatite containing different zinc concentrations and analysed the product using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and energy dispersive spectrometer (EDS). The biological assessment of Zn-HA was conducted by CCK-8 assay and bacterial inhibition tests. pH cycling was performed to estimate the effect of Zn-HA on the enamel surface after cold-light bleaching treatment. The XRD, FTIR, and EDS results illustrated that zinc ions and hydroxyapatite combined in two forms: (1) Zn2+ absorbed on the surface of HA crystal and (2) Zn2+ incorporated into the lattice of HA. The results indicated that 2% Zn-HA, 4% Zn-HA, and 8% Zn-HA effectively inhibited the growth of bacteria yet showed poor biocompatibility, whereas 1% Zn-HA positively affected osteoblast proliferation. The XRD and scanning electron microscopy (SEM) results showed that the use of Zn-HA in pH cycling is obviously beneficial for enamel remineralization. Zinc-substituted hydroxyapatite could be a promising biomaterial for use in cold-light bleaching to prevent enamel demineralization. PMID:29159178

Moessbauer studies in zinc-manganese ferrites for use in measuring small velocities and accelerations with great precision

NASA Technical Reports Server (NTRS)

Escue, W. T.; Gupta, R. G.; Mendiratta, R. G.

1975-01-01

Mossbauer spectroscopy was used for a systematic study of the magnetic behavior of manganese and zinc in mixed ferrites. It was observed that Zn2+ has preference to substitute Mn2+ at interstitial sites where the metal ions are tetrahedrally coordinated with four oxygen neighbors. The internal magnetic hyperfine field at the tetrahedral iron site is larger than that at the octahedral site. The relaxation effects were observed to play an important role as the zinc contents were increased, while the spin-correlation time and the magnetic field were observed to decrease in strength. It is concluded that Mossbauer effect data on complex materials, when used in conjunction with other data, can provide useful insight into the origin of the microscopic properties of magnetic materials.

Copper(II) and zinc(II) dinuclear enzymes model compounds: The nature of the metal ion in the biological function

NASA Astrophysics Data System (ADS)

Ferraresso, L. G.; de Arruda, E. G. R.; de Moraes, T. P. L.; Fazzi, R. B.; Da Costa Ferreira, A. M.; Abbehausen, C.

2017-12-01

First series transition metals are used abundantly by nature to perform catalytic transformations of several substrates. Furthermore, the cooperative activity of two proximal metal ions is common and represents a highly efficient catalytic system in living organisms. In this work three dinuclear μ-phenolate bridged metal complexes were prepared with copper(II) and zinc(II), resulting in a ZnZn, CuCu and CuZn with the ligand 2-ethylaminodimethylamino phenol (saldman) as model compounds of superoxide dismutase (CuCu and CuZn) and metallo-β-lactamases (ZnZn). Metals are coordinated in a μ-phenolate bridged symmetric system. Cu(II) presents a more distorted structure, while zinc is very symmetric. For this reason, [CuCu(saldman)] shows higher water solubility and also higher lability of the bridge. The antioxidant and hydrolytic beta-lactamase-like activity of the complexes were evaluated. The lability of the bridge seems to be important for the antioxidant activity and is suggested to because of [CuCu(saldman)] presents a lower antioxidant capacity than [CuZn(saldman)], which showed to present a more stable bridge in solution. The hydrolytic activity of the bimetallic complexes was assayed using nitrocefin as substrate and showed [ZnZn(saldman)] as a better catalyst than the Cu(II) analog. The series demonstrates the importance of the nature of the metal center for the biological function and how the reactivity of the model complex can be modulated by coordination chemistry.

Structural basis for the metal-selective activation of the manganese transport regulator of Bacillus subtilis.

PubMed

Kliegman, Joseph I; Griner, Sarah L; Helmann, John D; Brennan, Richard G; Glasfeld, Arthur

2006-03-21

The manganese transport regulator (MntR) of Bacillus subtilis is activated by Mn(2+) to repress transcription of genes encoding transporters involved in the uptake of manganese. MntR is also strongly activated by cadmium, both in vivo and in vitro, but it is poorly activated by other metal cations, including calcium and zinc. The previously published MntR.Mn(2+) structure revealed a binuclear complex of manganese ions with a metal-metal separation of 3.3 A (herein designated the AB conformer). Analysis of four additional crystal forms of MntR.Mn(2+) reveals that the AB conformer is only observed in monoclinic crystals at 100 K, suggesting that this conformation may be stabilized by crystal packing forces. In contrast, monoclinic crystals analyzed at room temperature (at either pH 6.5 or pH 8.5), and a second hexagonal crystal form (analyzed at 100 K), all reveal the shift of one manganese ion by 2.5 A, thereby leading to a newly identified conformation (the AC conformer) with an internuclear distance of 4.4 A. Significantly, the cadmium and calcium complexes of MntR also contain binuclear complexes with a 4.4 A internuclear separation. In contrast, the zinc complex of MntR contains only one metal ion per subunit, in the A site. Isothermal titration calorimetry confirms the stoichiometry of Mn(2+), Cd(2+), and Zn(2+) binding to MntR. We propose that the specificity of MntR activation is tied to productive binding of metal ions at two sites; the A site appears to act as a selectivity filter, determining whether the B or C site will be occupied and thereby fully activate MntR.

The Electronic Behavior of Zinc-Finger Protein Binding Sites in the Context of the DNA Extended Ladder Model

NASA Astrophysics Data System (ADS)

Oiwa, Nestor; Cordeiro, Claudette; Heermann, Dieter

2016-05-01

Instead of ATCG letter alignments, typically used in bioinformatics, we propose a new alignment method using the probability distribution function of the bottom of the occupied molecular orbital (BOMO), highest occupied molecular orbital (HOMO) and lowest unoccupied orbital (LUMO). We apply the technique to transcription factors with Cys2His2 zinc fingers. These transcription factors search for binding sites, probing for the electronic patterns at the minor and major DNA groves. The eukaryotic Cys2His2 zinc finger proteins bind to DNA ubiquitously at highly conserved domains. They are responsible for gene regulation and the spatial organization of DNA. To study and understand these zinc finger DNA-protein interactions, we use the extended ladder in the DNA model proposed by Zhu, Rasmussen, Balatsky & Bishop (2007) te{Zhu-2007}. Considering one single spinless electron in each nucleotide π-orbital along a double DNA chain (dDNA), we find a typical pattern for the bottom of BOMO, HOMO and LUMO along the binding sites. We specifically looked at two members of zinc finger protein family: specificity protein 1 (SP1) and early grown response 1 transcription factors (EGR1). When the valence band is filled, we find electrons in the purines along the nucleotide sequence, compatible with the electric charges of the binding amino acids in SP1 and EGR1 zinc finger.

DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure Function Study of the Zinc-Binding Domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akabayov, B.; Lee, S; Akabayov, S

2009-01-01

Synthesis of oligoribonucleotide primers for lagging-strand DNA synthesis in the DNA replication system of bacteriophage T7 is catalyzed by the primase domain of the gene 4 helicase-primase. The primase consists of a zinc-binding domain (ZBD) and an RNA polymerase (RPD) domain. The ZBD is responsible for recognition of a specific sequence in the ssDNA template whereas catalytic activity resides in the RPD. The ZBD contains a zinc ion coordinated with four cysteine residues. We have examined the ligation state of the zinc ion by X-ray absorption spectroscopy and biochemical analysis of genetically altered primases. The ZBD of primase engaged inmore » catalysis exhibits considerable asymmetry in coordination to zinc, as evidenced by a gradual increase in electron density of the zinc together with elongation of the zinc-sulfur bonds. Both wild-type primase and primase reconstituted from purified ZBD and RPD have a similar electronic change in the level of the zinc ion as well as the configuration of the ZBD. Single amino acid replacements in the ZBD (H33A and C36S) result in the loss of both zinc binding and its structural integrity. Thus the zinc in the ZBD may act as a charge modulation indicator for the surrounding sulfur atoms necessary for recognition of specific DNA sequences.« less

Accounting for both local aquatic community composition and bioavailability in setting site-specific quality standards for zinc.

PubMed

Peters, Adam; Simpson, Peter; Moccia, Alessandra

2014-01-01

Recent years have seen considerable improvement in water quality standards (QS) for metals by taking account of the effect of local water chemistry conditions on their bioavailability. We describe preliminary efforts to further refine water quality standards, by taking account of the composition of the local ecological community (the ultimate protection objective) in addition to bioavailability. Relevance of QS to the local ecological community is critical as it is important to minimise instances where quality classification using QS does not reconcile with a quality classification based on an assessment of the composition of the local ecology (e.g. using benthic macroinvertebrate quality assessment metrics such as River InVertebrate Prediction and Classification System (RIVPACS)), particularly where ecology is assessed to be at good or better status, whilst chemical quality is determined to be failing relevant standards. The alternative approach outlined here describes a method to derive a site-specific species sensitivity distribution (SSD) based on the ecological community which is expected to be present at the site in the absence of anthropogenic pressures (reference conditions). The method combines a conventional laboratory ecotoxicity dataset normalised for bioavailability with field measurements of the response of benthic macroinvertebrate abundance to chemical exposure. Site-specific QSref are then derived from the 5%ile of this SSD. Using this method, site QSref have been derived for zinc in an area impacted by historic mining activities. Application of QSref can result in greater agreement between chemical and ecological metrics of environmental quality compared with the use of either conventional (QScon) or bioavailability-based QS (QSbio). In addition to zinc, the approach is likely to be applicable to other metals and possibly other types of chemical stressors (e.g. pesticides). However, the methodology for deriving site-specific targets requires

Zinc phosphate conversion coatings

DOEpatents

Sugama, T.

1997-02-18

Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate {alpha}-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal. 33 figs.

Polyacrylamide Gel-Contained Zinc Finger Peptide as the "Lock" and Zinc Ions as the "Key" for Construction of Ultrasensitive Prostate-Specific Antigen SERS Immunosensor.

PubMed

Xie, Linglin; Yang, Xia; He, Yi; Yuan, Ruo; Chai, Yaqin

2018-05-02

In this work, we adopted polyacrylamide gel-contained zinc finger peptide (PZF) as a "lock" of Raman signal and zinc ions (Zn 2+ ) as a sensitive "key", which was converted from target-captured ZnO NPs, to achieve the measurement of prostate-specific antigen (PSA). Owing to the lock effect from PZF, the surface-enhanced Raman scattering (SERS) tag toluidine blue (TB) connected on Ag NP-coating silica wafer was sheltered leading to low Raman response. Meanwhile, target PSA can specifically connect with antibody 2-coupled ZnO nanocomplexes (ZnO@Au@Ab 2 ) and antibody 1-coupled magnetic (CoFe 2 O 4 @Au@Ab 1 ) nanocomposite through sandwich immunoassay. In the presence of HCl, the ZnO NPs would convert into Zn 2+ to open the PZF because Zn 2+ can specifically react with zinc finger peptide to destroy the PZF structure forming abundant pores. In this way, Zn 2+ could act as the key of Raman signal to open the PZF structure obtaining a strong Raman signal of TB. The proposed SERS sensor can have a quantitative detection of PSA within the range of 1 pg mL -1 to 10 ng mL -1 with a detection limit of 0.65 pg mL -1 . The interaction between zinc finger peptide and Zn 2+ was firstly applied in SERS sensor for the sensitive detection of PSA. These results demonstrated that the new designed SERS biosensor could be a promising tool in biomarker diagnosis.

Zinc phthalocyanine nanowires based flexible sensor for room temperature Cl2 detection

NASA Astrophysics Data System (ADS)

Devi, Pooja; Saini, Rajan; Singh, Rajinder; Mahajan, A.; Bedi, R. K.; Aswal, D. K.; Debnath, A. K.

2018-04-01

We have fabricated highly sensitive and Cl2 selective flexible sensor by depositing solution processed zinc phthalocyanine nanowires onto the flexible PET substrate and studied its Cl2 sensing characteristics in Cl2 concentration range 5-1500 ppb. The flexible sensor has a minimum detection limit as low as 5 ppb of Cl2 and response as high as 550% within 10 seconds. Interestingly, the sensor exhibited enhanced and faster response kinetics under bending conditions. The gas sensing mechanism of sensor has been discussed on the basis of XPS and Raman spectroscopic studies which revealed that zinc ions were the preferred sites for Cl2 interactions.

Comment on "Active sites for CO2 hydrogenation to methanol on Cu/ZnO catalysts".

PubMed

Nakamura, Junji; Fujitani, Tadahiro; Kuld, Sebastian; Helveg, Stig; Chorkendorff, Ib; Sehested, Jens

2017-09-01

Kattel et al (Reports, 24 March 2017, p. 1296) report that a zinc on copper (Zn/Cu) surface undergoes oxidation to zinc oxide/copper (ZnO/Cu) during carbon dioxide (CO 2 ) hydrogenation to methanol and conclude that the Cu-ZnO interface is the active site for methanol synthesis. Similar experiments conducted two decades ago by Fujitani and Nakamura et al demonstrated that Zn is attached to formate rather than being fully oxidized. Copyright © 2017, American Association for the Advancement of Science.

Elaboration and characterization of solid materials of types zeolite NaA and faujasite NaY exchanged by zinc metallic ions Zn2+

NASA Astrophysics Data System (ADS)

Nibou, D.; Amokrane, S.; Mekatel, H.; Lebaili, N.

2009-11-01

The present work deals with the elaborated of NaA and faujasite NaY solid materials according to a hydrothermal crystallization of amorphous gels composed of solutions of silicon, aluminum and sodium. The process elaboration has been achieved in autoclaves made of steel lined in Teflon under different operating conditions of temperature of heating, time of contact and stirring. After crystallization, the samples were characterized by different techniques such as X ray diffraction, scanning electronic microscopy, infrared spectroscopy, thermal analysis, and chemical analysis. Pure solid materials NaA and NaY zeolites were obtained and were impregnated by (Zn2+) ions by ion exchange process. The effects of various parameters such as initial metal concentration, pH, solid-liquid ratio (R) and temperature on the exchange percentage are studied. The equilibrium isotherms of zinc ions sorption are also evaluated using Langmuir and Freundlich models. Thermodynamic parameters, i.e. enthalpy of adsorption ΔHads∘, entropy change ΔSads∘ and Gibbs free energy ΔGads∘ for the sorption of zinc ions on NaA and NaY zeolites were examined.

Effect of doping with nickel ions on the structural state of a zinc oxide crystal

NASA Astrophysics Data System (ADS)

Dubinin, S. F.; Sokolov, V. I.; Parkhomenko, V. D.; Maksimov, V. I.; Gruzdev, N. B.

2009-10-01

The fine structure of a hexagonal zinc oxide crystal doped with nickel ions of the composition Zn1 - x Ni x O has been studied using neutron diffraction and magnetic measurements. It is established that even at very low doping levels ( x = 0.0004), the crystal undergoes local distortions in basal planes of the initial hexagonal lattice. The local distortions are assumed to be sources of the formation of ferromagnetism in compounds of this class.

Effects of mouthrinses with chlorhexidine and zinc ions combined with fluoride on the viability and glycolytic activity of dental plaque.

PubMed

Giertsen, E; Scheie, A A

1995-10-01

Inhibition of plaque acidogenicity by a mouthrinse with chlorhexidine (CHX) or zinc ions has been ascribed to a prolonged bacteriostasis due to substantive properties of the agents. The present aim was to study the effects of mouthrinses with CHX and Zn ions combined with fluoride on the viability and glycolytic activity of dental plaque in order to assess the bacteriostatic versus possible bactericidal effects. Following 2 d of plaque accumulation, 4 groups of 10 students rinsed with either 12 mM NaF (F), 0.55 mM CHX diacetate+F (F-CHX), 10 mM Zn acetate+F (F-Zn), or with the three agents in combination (F-CHX-Zn). Plaque samples were collected before and 90 min after mouthrinsing. Thereafter, the in vivo plaque pH response to sucrose was monitored in each student using touch microelectrodes. F-CHX and F-CHX-Zn reduced the in vivo pH fall significantly as compared with F, whereas F-Zn exerted a non-significant inhibition. Pooled pre- and post-rinse plaque samples were used to measure the pH fall during fermentation of [14C]-glucose, and the glycolytic profiles were analyzed by HPLC. Bacterial viability was assessed by counting the colony-forming units (CFU). All mouthrinses except F reduced glucose consumption and acid formation and thus the pH fall. F-CHX reduced the CFU equal to the reduction of glucose consumption, indicating that inhibition of plaque acidogenicity was due to a bactericidal rather than a bacteriostatic effect. F and F-Zn did not reduce the CFU, thus F-Zn decreased glucose metabolism without affecting plaque viability. F-CHX-Zn reduced both the CFU and glucose metabolism of surviving plaque microorganisms.

Improved zinc electrode and rechargeable zinc-air battery

DOEpatents

Ross, P.N. Jr.

1988-06-21

The invention comprises an improved rechargeable zinc-air cell/battery having recirculating alkaline electrolyte and a zinc electrode comprising a porous foam support material which carries the active zinc electrode material. 5 figs.

Biomarkers of metals exposure in fish from lead-zinc mining areas of Southeastern Missouri, USA

USGS Publications Warehouse

Schmitt, C.J.; Whyte, J.J.; Roberts, A.P.; Annis, M.L.; May, T.W.; Tillitt, D.E.

2007-01-01

The potential effects of proposed lead-zinc mining in an ecologically sensitive area were assessed by studying a nearby mining district that has been exploited for about 30 y under contemporary environmental regulations and with modern technology. Blood and liver samples representing fish of three species (largescale stoneroller, Campostoma oligolepis, n=91; longear sunfish, Lepomis megalotis, n=105; and northern hog sucker, Hypentelium nigricans, n=20) from 16 sites representing a range of conditions relative to mining activities were collected. Samples were analyzed for metals (also reported in a companion paper) and for biomarkers of metals exposure [erythrocyte ??-aminolevulinic acid dehydratase (ALA-D) activity; concentrations of zinc protoporphyrin (ZPP), iron, and hemoglobin (Hb) in blood; and hepatic metallothionein (MT) gene expression and lipid peroxidation]. Blood lead concentrations were significantly higher and ALA-D activity significantly lower in all species at sites nearest to active lead-zinc mines and in a stream contaminated by historical mining than at reference or downstream sites. ALA-D activity was also negatively correlated with blood lead concentrations in all three species but not with other metals. Iron and Hb concentrations were positively correlated in all three species, but were not correlated with any other metals in blood or liver in any species. MT gene expression was positively correlated with liver zinc concentrations, but neither MT nor lipid peroxidase differences among fish grouped according to lead concentrations were statistically significant. ZPP was not detected by hematofluorometry in most fish, but fish with detectable ZPP were from sites affected by mining. Collectively, these results confirm that metals are released to streams from active lead-zinc mining sites and are accumulated by fish. ?? 2007 Elsevier Inc. All rights reserved.

Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes.

PubMed

Csermely, P; Szamel, M; Resch, K; Somogyi, J

1988-05-15

In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested (Parker, P.J., Coussens, L., Totty, N., Rhee, L., Young, S., Chen, E., Stabel, S., Waterfield, M.D., and Ullrich, A. (1986) Science 233, 853-859). In the present report, we demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes, and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn2+, while Fe2+ and Mn2+ are only partially counteractive. Our results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca2+, phorbol ester, or antigen.

Aqueous rechargeable zinc/sodium vanadate batteries with enhanced performance from simultaneous insertion of dual carriers.

PubMed

Wan, Fang; Zhang, Linlin; Dai, Xi; Wang, Xinyu; Niu, Zhiqiang; Chen, Jun

2018-04-25

Rechargeable aqueous zinc-ion batteries are promising energy storage devices due to their high safety and low cost. However, they remain in their infancy because of the limited choice of positive electrodes with high capacity and satisfactory cycling performance. Furthermore, their energy storage mechanisms are not well established yet. Here we report a highly reversible zinc/sodium vanadate system, where sodium vanadate hydrate nanobelts serve as positive electrode and zinc sulfate aqueous solution with sodium sulfate additive is used as electrolyte. Different from conventional energy release/storage in zinc-ion batteries with only zinc-ion insertion/extraction, zinc/sodium vanadate hydrate batteries possess a simultaneous proton, and zinc-ion insertion/extraction process that is mainly responsible for their excellent performance, such as a high reversible capacity of 380 mAh g -1 and capacity retention of 82% over 1000 cycles. Moreover, the quasi-solid-state zinc/sodium vanadate hydrate battery is also a good candidate for flexible energy storage device.

Zinc and copper status of women by physical activity and menstrual status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, A.; Deuster, P.A.; Kyle, S.B.

The zinc and copper status of 33 eumenorrheic (EU) and 12 amenorrheic (AM) female marathon runners and 19 EU and 8 AM nonrunners were determined from 3-day diet records and plasma and erythrocyte (RBC) levels. The study was conducted as a completely randomized 2 x 2 factorial. Mean daily zinc intakes of all groups fell below the recommended dietary allowances. Copper intakes of runners (EU = 1.3 mg; AM = 1.3 mg) were not significantly different. Menstrual status did not affect plasma zinc, RBC zinc or plasma copper levels. Physical activity however, affected RBC zinc and plasma copper levels. Bothmore » these parameters were significantly higher in runners. These findings suggest that exercise influences blood zinc and copper levels.« less

Chelatable trace zinc causes low, irreproducible KDAC8 activity.

PubMed

Toro, Tasha B; Edenfield, Samantha A; Hylton, Brandon J; Watt, Terry J

2018-01-01

Acetylation is an important regulatory mechanism in cells, and emphasis is being placed on identifying substrates and small molecule modulators of this post-translational modification. However, the reported in vitro activity of the lysine deacetylase KDAC8 is inconsistent across experimental setups, even with the same substrate, complicating progress in the field. We detected trace levels of zinc, a known inhibitor of KDAC8 when present in excess, even in high-quality buffer reagents, at concentrations that are sufficient to significantly inhibit the enzyme under common reaction conditions. We hypothesized that trace zinc in solution could account for the observed variability in KDAC8 activity. We demonstrate that addition of chelators, including BSA, EDTA, and citrate, and/or the use of a phosphate-based buffer instead of the more common tris-based buffer, eliminates the inhibition from low levels of zinc as well as the dependence of specific activity on enzyme concentration. This results in high KDAC8 activity that is consistent across buffer systems, even using low concentrations of enzyme. We report conditions that are suitable for several assays to increase both enzyme activity and reproducibility. Our results have significant implications for approaches used to identify substrates and small molecule modulators of KDAC8 and interpretation of existing data. Copyright © 2017 Elsevier Inc. All rights reserved.

Computational exploration of zinc binding groups for HDAC inhibition.

PubMed

Chen, Kai; Xu, Liping; Wiest, Olaf

2013-05-17

Histone deacetylases (HDACs) have emerged as important drug targets in epigenetics. The most common HDAC inhibitors use hydroxamic acids as zinc binding groups despite unfavorable pharmacokinetic properties. A two-stage protocol of M05-2X calculations of a library of 48 fragments in a small model active site, followed by QM/MM hybrid calculations of the full enzyme with selected binders, is used to prospectively select potential bidentate zinc binders. The energetics and interaction patterns of several zinc binders not previously used for the inhibition of HDACs are discussed.

Zinc promotes proliferation and activation of myogenic cells via the PI3K/Akt and ERK signaling cascade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohashi, Kazuya, E-mail: asuno10k@yahoo.co.jp; Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp; Wada, Eiji, E-mail: gacchu1@yahoo.co.jp

2015-05-01

Skeletal muscle stem cells named muscle satellite cells are normally quiescent but are activated in response to various stimuli, such as injury and overload. Activated satellite cells enter the cell cycle and proliferate to produce a large number of myogenic progenitor cells, and these cells then differentiate and fuse to form myofibers. Zinc is one of the essential elements in the human body, and has multiple roles, including cell growth and DNA synthesis. However, the role of zinc in myogenic cells is not well understood, and is the focus of this study. We first examined the effects of zinc onmore » differentiation of murine C2C12 myoblasts and found that zinc promoted proliferation, with an increased number of cells incorporating EdU, but inhibited differentiation with reduced myogenin expression and myotube formation. Furthermore, we used the C2C12 reserve cell model of myogenic quiescence to investigate the role of zinc on activation of myogenic cells. The number of reserve cells incorporating BrdU was increased by zinc in a dose dependent manner, with the number dramatically further increased using a combination of zinc and insulin. Akt and extracellular signal-regulated kinase (ERK) are downstream of insulin signaling, and both were phosphorylated after zinc treatment. The zinc/insulin combination-induced activation involved the phosphoinositide 3-kinase (PI3K)/Akt and ERK cascade. We conclude that zinc promotes activation and proliferation of myogenic cells, and this activation requires phosphorylation of PI3K/Akt and ERK as part of the signaling cascade. - Highlights: • Zinc has roles for promoting proliferation and inhibition differentiation of C2C12. • Zinc promotes activation of reserve cells. • Insulin and zinc synergize activation of reserve cells. • PI3K/Akt and ERK cascade affect zinc/insulin-mediated activation of reserve cells.« less

In vitro evaluation of cellular responses induced by ZnO nanoparticles, zinc ions and bulk ZnO in fish cells.

PubMed

Fernández, Dolores; García-Gómez, Concepción; Babín, Mar

2013-05-01

Zinc oxide nanoparticles (ZnO-NPs) are inevitably released into the environment and are potentially dangerous for aquatic life. However, the potential mechanisms of cytotoxicity of zinc nanoparticles remain unclear. Studying the toxicity of ZnO-NPs with In vitro systems will help to determine their interactions with cellular biomolecules. The aim of this study was to evaluate the cytotoxic potentials of ZnO-NPs in established fish cell lines (RTG-2, RTH-149 and RTL-W1) and compare them with those of bulk ZnO and Zn(2+) ions. Membrane function (CFDA-AM assay), mitochondrial function (MTT assay), cell growth (KBP assay), cellular stress (β-galactosidase assay), reductase enzyme activity (AB assay), reactive oxygen species (ROS), total glutathione cellular content (tGSH assay) and glutathione S-transferase (GST) activities were assessed for all cell lines. ZnO-NPs cytotoxicity was greater than those of bulk ZnO and Zn(2+). ZnO-NPs induced oxidative stress is dependent on their dose. Low cost tests, such as CFDA-AM, ROS, GST activity and tGSH cell content test that use fish cell lines, may be used to detect oxidative stress and redox status changes. Particle dissolution of the ZnO-NPs did not appear to play an important role in the observed toxicity in this study. Published by Elsevier B.V.

Optical studies of Sm³⁺ ions doped zinc alumino bismuth borate glasses.

PubMed

Swapna, K; Mahamuda, Sk; Srinivasa Rao, A; Shakya, S; Sasikala, T; Haranath, D; Vijaya Prakash, G

2014-05-05

Zinc Alumino Bismuth Borate (ZnAlBiB) glasses doped with different concentrations of samarium (Sm(3+)) ions were prepared by using melt quenching technique and characterized for their lasing potentialities in visible region by using the techniques such as optical absorption, emission and emission decay measurements. Radiative properties for various fluorescent levels of Sm(3+) ions were estimated from absorption spectral information using Judd-Ofelt (JO) analysis. The emission spectra and con-focal photoluminescence images obtained by 410 nm laser excitation demonstrates very distinct and intense orange-red emission for all the doped glasses. The suitable concentration of Sm(3+) ions in these glasses to act as an efficient lasing material has been discussed by measuring the emission cross-section and branching ratios for the emission transitions. The quantum efficiencies were also been estimated from emission decay measurements recorded for the (4)G5/2 level of Sm(3+) ions. From the measured emission cross-sections, branching ratios, strong photoluminescence features and CIE chromaticity coordinates, it was found that 1 mol% of Sm(3+) ions doped ZnAlBiB glasses are most suitable for the development of visible orange-red lasers. Copyright © 2014 Elsevier B.V. All rights reserved.

Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding.

PubMed

Gennadios, Heather A; Christianson, David W

2006-12-26

LpxC is a zinc metalloenzyme that catalyzes the first committed step in the biosynthesis of lipid A, a vital component of the outer membrane of Gram-negative bacteria. Accordingly, the inhibition of LpxC is an attractive strategy for the treatment of Gram-negative bacterial infections. Here, we report the 2.7 A resolution X-ray crystal structure of LpxC from Aquifex aeolicus complexed with uridine 5'-diphosphate (UDP), and the 3.1 A resolution structure of LpxC complexed with pyrophosphate. The X-ray crystal structure of the LpxC-UDP complex provides the first view of interactions likely to be exploited by the substrate UDP group in the "basic patch" of the active site. The diphosphate group of UDP makes hydrogen bond interactions with strictly conserved residue K239 as well as solvent molecules. The ribose moiety of UDP interacts with partially conserved residue E197. The UDP uracil group hydrogen bonds with both the backbone NH group and the backbone carbonyl group of E160, and with the backbone NH group of K162 through an intervening water molecule. Finally, the alpha-phosphate and uracil groups of UDP interact with R143 and R262 through intervening water molecules. The structure of LpxC complexed with pyrophosphate reveals generally similar intermolecular interactions in the basic patch. Unexpectedly, diphosphate binding in both complexes is accompanied by coordination to an additional zinc ion, resulting in the identification of a new metal-binding site termed the E-site. The structures of the LpxC-UDP and LpxC-pyrophosphate complexes provide new insights with regard to substrate recognition in the basic patch and metal ion coordination in the active site of LpxC.

Active membrane having uniform physico-chemically functionalized ion channels

DOEpatents

Gerald, II, Rex E; Ruscic, Katarina J; Sears, Devin N; Smith, Luis J; Klingler, Robert J; Rathke, Jerome W

2012-09-24

The present invention relates to a physicochemically-active porous membrane for electrochemical cells that purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. One dimension of the pore surface has a macroscopic length (1 nm-1000 .mu.m) and is directed parallel to the direction of an electric field, which is produced between the cathode and the anode electrodes of an electrochemical cell. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats.

PubMed

Nazarizadeh, Ali; Asri-Rezaie, Siamak

2016-08-01

In the current study, antidiabetic activity and toxic effects of zinc oxide nanoparticles (ZnO) were investigated in diabetic rats compared to zinc sulfate (ZnSO4) with particular emphasis on oxidative stress parameters. One hundred and twenty male Wistar rats were divided into two healthy and diabetic groups, randomly. Each major group was further subdivided into five subgroups and then orally supplemented with various doses of ZnO (1, 3, and 10 mg/kg) and ZnSO4 (30 mg/kg) for 56 consecutive days. ZnO showed greater antidiabetic activity compared to ZnSO4 evidenced by improved glucose disposal, insulin levels, and zinc status. The altered activities of erythrocyte antioxidant enzymes as well as raised levels of lipid peroxidation and a marked reduction of total antioxidant capacity were observed in rats receiving ZnO. ZnO nanoparticles acted as a potent antidiabetic agent, however, severely elicited oxidative stress particularly at higher doses.

Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation

PubMed Central

Wong, Carmen P.; Rinaldi, Nicole A.; Ho, Emily

2015-01-01

Scope Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age-related immune defects, including chronic inflammation, coincide with declining zinc status. Methods and results An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency up-regulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, that coincided with increased IL1β and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals. Conclusion Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation. PMID:25656040

Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.

PubMed

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P; Lewis, Timothy A; Maglathin, Rebecca L; McLean, Thomas H; Bochkarev, Alexey; Plotnikov, Alexander N; Vedadi, Masoud; Arrowsmith, Cheryl H

2008-04-25

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

Evaluation of layered zinc hydroxide nitrate and zinc/nickel double hydroxide salts in the removal of chromate ions from solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bortolaz de Oliveira, Henrique; Wypych, Fernando, E-mail: wypych@ufpr.br

Layered zinc hydroxide nitrate (ZnHN) and Zn/Ni layered double hydroxide salts were synthesized and used to remove chromate ions from solutions at pH 8.0. The materials were characterized by many instrumental techniques before and after chromate ion removal. ZnHN decomposed after contact with the chromate solution, whereas the layered structure of Zn/Ni hydroxide nitrate (Zn/NiHN) and Zn/Ni hydroxide acetate (Zn/NiHA) remained their layers intact after the topotactic anionic exchange reaction, only changing the basal distances. ZnHN, Zn/NiHN, and Zn/NiHA removed 210.1, 144.8, and 170.1 mg of CrO{sub 4}{sup 2−}/g of material, respectively. Although the removal values obtained for Zn/NiHN andmore » Zn/NiHA were smaller than the values predicted for the ideal formulas of the solids (194.3 and 192.4 mg of CrO{sub 4}{sup 2−}/g of material, respectively), the measured capacities were higher than the values achieved with many materials reported in the literature. Kinetic experiments showed the removal reaction was fast. To facilitate the solid/liquid separation process after chromium removal, Zn/Ni layered double hydroxide salts with magnetic supports were also synthesized, and their ability to remove chromate was evaluated. - Highlights: • Zinc hydroxide nitrate and Zn/Ni hydroxide nitrate or acetate were synthesized. • The interlayer anions were replaced by chromate anions at pH=8.0. • Only Zn/Ni hydroxide nitrate or acetate have the structure preserved after exchange. • Fast exchange reaction and high capacity of chromate removal were observed. • Magnetic materials were obtained to facilitate the solids removal the from solutions.« less

Optical properties of zinc borotellurite glass doped with trivalent dysprosium ion

NASA Astrophysics Data System (ADS)

Ami Hazlin, M. N.; Halimah, M. K.; Muhammad, F. D.; Faznny, M. F.

2017-04-01

The zinc borotellurite doped with dysprosium oxide glass samples with chemical formula {[(TeO2) 0 . 7(B2O3) 0 . 3 ] 0 . 7(ZnO) 0 . 3 } 1 - x(Dy2O3)x (where x=0.01, 0.02, 0.03, 0.04 and 0.05 M fraction) were prepared by using conventional melt quenching technique. The structural and optical properties of the proposed glass systems were characterized by using X-ray diffraction (XRD) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, and UV-VIS spectroscopy. The amorphous nature of the glass systems is confirmed by using XRD technique. The infrared spectra of the glass systems indicate three obvious absorption bands which are assigned to BO3 and TeO4 vibrational groups. Based on the absorption spectra obtained, the direct and indirect optical band gaps, as well as the Urbach energy were calculated. It is observed that both the direct and indirect optical band gaps increase with the concentration of Dy3+ ions. On the other hand, the Urbach energy is observed to decrease as the concentration of Dy3+ ions increases.

Applications of Nanomaterials Based on Magnetite and Mesoporous Silica on the Selective Detection of Zinc Ion in Live Cell Imaging.

PubMed

Erami, Roghayeh Sadeghi; Ovejero, Karina; Meghdadi, Soraia; Filice, Marco; Amirnasr, Mehdi; Rodríguez-Diéguez, Antonio; De La Orden, María Ulagares; Gómez-Ruiz, Santiago

2018-06-14

Functionalized magnetite nanoparticles (FMNPs) and functionalized mesoporous silica nanoparticles (FMSNs) were synthesized by the conjugation of magnetite and mesoporous silica with the small and fluorogenic benzothiazole ligand, that is, 2(2-hydroxyphenyl)benzothiazole ( hpbtz ). The synthesized fluorescent nanoparticles were characterized by FTIR, XRD, XRF, 13 C CP MAS NMR, BET, and TEM. The photophysical behavior of FMNPs and FMSNs in ethanol was studied using fluorescence spectroscopy. The modification of magnetite and silica scaffolds with the highly fluorescent benzothiazole ligand enabled the nanoparticles to be used as selective and sensitive optical probes for zinc ion detection. Moreover, the presence of hpbtz in FMNPs and FMSNs induced efficient cell viability and zinc ion uptake, with desirable signaling in the normal human kidney epithelial (Hek293) cell line. The significant viability of FMNPs and FMSNs (80% and 92%, respectively) indicates a potential applicability of these nanoparticles as in vitro imaging agents. The calculated limit of detections (LODs) were found to be 2.53 × 10 −6 and 2.55 × 10 −6 M for Fe₃O₄-H@hpbtz and MSN-Et₃N-IPTMS-hpbtz-f1, respectively. FMSNs showed more pronounced zinc signaling relative to FMNPs, as a result of the more efficient penetration into the cells.

Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis.

PubMed

Hara, Takafumi; Takeda, Taka-Aki; Takagishi, Teruhisa; Fukue, Kazuhisa; Kambe, Taiho; Fukada, Toshiyuki

2017-03-01

Zinc (Zn) is an essential trace mineral that regulates the expression and activation of biological molecules such as transcription factors, enzymes, adapters, channels, and growth factors, along with their receptors. Zn deficiency or excessive Zn absorption disrupts Zn homeostasis and affects growth, morphogenesis, and immune response, as well as neurosensory and endocrine functions. Zn levels must be adjusted properly to maintain the cellular processes and biological responses necessary for life. Zn transporters regulate Zn levels by controlling Zn influx and efflux between extracellular and intracellular compartments, thus, modulating the Zn concentration and distribution. Although the physiological functions of the Zn transporters remain to be clarified, there is growing evidence that Zn transporters are related to human diseases, and that Zn transporter-mediated Zn ion acts as a signaling factor, called "Zinc signal". Here we describe critical roles of Zn transporters in the body and their contribution at the molecular, biochemical, and genetic levels, and review recently reported disease-related mutations in the Zn transporter genes.

Tailoring nanoscopic confines to maximize catalytic activity of hydronium ions

NASA Astrophysics Data System (ADS)

Shi, Hui; Eckstein, Sebastian; Vjunov, Aleksei; Camaioni, Donald M.; Lercher, Johannes A.

2017-05-01

Acid catalysis by hydronium ions is ubiquitous in aqueous-phase organic reactions. Here we show that hydronium ion catalysis, exemplified by intramolecular dehydration of cyclohexanol, is markedly influenced by steric constraints, yielding turnover rates that increase by up to two orders of magnitude in tight confines relative to an aqueous solution of a Brønsted acid. The higher activities in zeolites BEA and FAU than in water are caused by more positive activation entropies that more than offset higher activation enthalpies. The higher activity in zeolite MFI with pores smaller than BEA and FAU is caused by a lower activation enthalpy in the tighter confines that more than offsets a less positive activation entropy. Molecularly sized pores significantly enhance the association between hydronium ions and alcohols in a steric environment resembling the constraints in pockets of enzymes stabilizing active sites.

Seasonal and spatial patterns of metals at a restored copper mine site. I. Stream copper and zinc

USGS Publications Warehouse

Bambic, D.G.; Alpers, Charles N.; Green, P.G.; Fanelli, E.; Silk, W.K.

2006-01-01

Seasonal and spatial variations in metal concentrations and pH were found in a stream at a restored copper mine site located near a massive sulfide deposit in the Foothill copper-zinc belt of the Sierra Nevada, California. At the mouth of the stream, copper concentrations increased and pH decreased with increased streamflow after the onset of winter rain and, unexpectedly, reached extreme values 1 or 2 months after peaks in the seasonal hydrographs. In contrast, aqueous zinc and sulfate concentrations were highest during low-flow periods. Spatial variation was assessed in 400 m of reach encompassing an acidic, metal-laden seep. At this seep, pH remained low (2-3) throughout the year, and copper concentrations were highest. In contrast, the zinc concentrations increased with downstream distance. These spatial patterns were caused by immobilization of copper by hydrous ferric oxides in benthic sediments, coupled with increasing downstream supply of zinc from groundwater seepage.

Mutation of a Zinc-Binding Residue in the Glycine Receptor α1 Subunit Changes Ethanol Sensitivity In Vitro and Alcohol Consumption In Vivo

PubMed Central

McCracken, Lindsay M.; Blednov, Yuri A.; Trudell, James R.; Benavidez, Jillian M.; Betz, Heinrich

2013-01-01

Ethanol is a widely used drug, yet an understanding of its sites and mechanisms of action remains incomplete. Among the protein targets of ethanol are glycine receptors (GlyRs), which are potentiated by millimolar concentrations of ethanol. In addition, zinc ions also modulate GlyR function, and recent evidence suggests that physiologic concentrations of zinc enhance ethanol potentiation of GlyRs. Here, we first built a homology model of a zinc-bound GlyR using the D80 position as a coordination site for a zinc ion. Next, we investigated in vitro the effects of zinc on ethanol action at recombinant wild-type (WT) and mutant α1 GlyRs containing the D80A substitution, which eliminates zinc potentiation. At D80A GlyRs, the effects of 50 and 200 mM ethanol were reduced as compared with WT receptors. Also, in contrast to what was seen with WT GlyRs, neither adding nor chelating zinc changed the magnitude of ethanol enhancement of mutant D80A receptors. Next, we evaluated the in vivo effects of the D80A substitution by using heterozygous Glra1(D80A) knock-in (KI) mice. The KI mice showed decreased ethanol consumption and preference, and they displayed increased startle responses compared with their WT littermates. Other behavioral tests, including ethanol-induced motor incoordination and strychnine-induced convulsions, revealed no differences between the KI and WT mice. Together, our findings indicate that zinc is critical in determining the effects of ethanol at GlyRs and suggest that zinc binding at the D80 position may be important for mediating some of the behavioral effects of ethanol action at GlyRs. PMID:23230213

Physical chemical effects of zinc on in vitro enamel demineralization.

PubMed

Mohammed, N R; Mneimne, M; Hill, R G; Al-Jawad, M; Lynch, R J M; Anderson, P

2014-09-01

Zinc salts are formulated into oral health products as antibacterial agents, yet their interaction with enamel is not clearly understood. The aim was to investigate the effect of zinc concentration [Zn(2+)] on the in vitro demineralization of enamel during exposure to caries-simulating conditions. Furthermore, the possible mechanism of zinc's action for reducing demineralization was determined. Enamel blocks and synthetic hydroxyapatite (HAp) were demineralized in a range of zinc-containing acidic solutions (0-3565ppm [Zn(2+)]) at pH 4.0 and 37°C. Inductively coupled-plasma optical emission spectroscopy (ICP-OES) was used to measure ion release into solution. Enamel blocks were analysed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), and HAp by X-ray diffraction (XRD) and neutron diffraction (ND). ICP-OES analysis of the acidic solutions showed a decrease in [Ca(2+)] and [PO4(3-)] release with increasing [Zn(2+)]. FTIR revealed a α-hopeite (α-Zn3(PO4)2.4H2O)-like phase on the enamel surfaces at >107ppm [Zn(2+)]. XRD and ND analysis confirmed a zinc-phosphate phase present alongside the HAp. This study confirms that zinc reduces enamel demineralization. Under the conditions studied, zinc acts predominantly on enamel surfaces at PO4(3-) sites in the HAp lattice to possibly form an α-hopeite-like phase. These results have a significant implication on the understanding of the fundamental chemistry of zinc in toothpastes and demonstrate its therapeutic potential in preventing tooth mineral loss. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Zinc Interactions With Brain-Derived Neurotrophic Factor and Related Peptide Fragments.

PubMed

Travaglia, A; La Mendola, D

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal development and survival, synaptic plasticity, and cognitive function. Dysregulation of BDNF signaling is involved in several neurodegenerative disorders, including Alzheimer's disease. Alteration of metal ion homeostasis is observed both in normal aging and in many neurodegenerative diseases. Interestingly, there is a significant overlap between brain areas characterized by metal ion dyshomeostasis and those where BDNF exerts its biological activity. Therefore, it is reasonable to speculate that metal ions, especially zinc, can modulate the activity of BDNF. The synthesis of BDNF peptidomimetic can be helpful both to understand the molecular interaction of BDNF with metal ions and to develop new drugs for neurodegenerative diseases. © 2017 Elsevier Inc. All rights reserved.

A structure-based virtual screening approach toward the discovery of histone deacetylase inhibitors: identification of promising zinc-chelating groups.

PubMed

Park, Hwangseo; Kim, Sukyoung; Kim, Yong Eun; Lim, Soo-Jeong

2010-04-06

The inhibitors of histone deacetylases (HDACs) have drawn a great deal of attention due to their promising potential as small-molecule therapeutics for the treatment of cancer. By means of virtual screening with docking simulations under consideration of the effects of ligand solvation, we were able to identify six novel HDAC inhibitors with IC(50) values ranging from 1 to 100 muM. These newly identified inhibitors are structurally diverse and have various chelating groups for the active site zinc ion, including N-[1,3,4]thiadiazol-2-yl sulfonamide, N-thiazol-2-yl sulfonamide, and hydroxamic acid moieties. The former two groups are included in many drugs in current clinical use and have not yet been reported as HDAC inhibitors. Therefore, they can be considered as new inhibitor scaffolds for the development of anticancer drugs by structure-activity relationship studies to improve the inhibitory activities against HDACs. Interactions with the HDAC1 active site residues responsible for stabilizing these new inhibitors are addressed in detail.

Zinc and Copper Effects on Stability of Tubulin and Actin Networks in Dendrites and Spines of Hippocampal Neurons.

PubMed

Perrin, Laura; Roudeau, Stéphane; Carmona, Asuncion; Domart, Florelle; Petersen, Jennifer D; Bohic, Sylvain; Yang, Yang; Cloetens, Peter; Ortega, Richard

2017-07-19

Zinc and copper ions can modulate the activity of glutamate receptors. However, labile zinc and copper ions likely represent only the tip of the iceberg and other neuronal functions are suspected for these metals in their bound state. We performed synchrotron X-ray fluorescence imaging with 30 nm resolution to image total biometals in dendrites and spines from hippocampal neurons. We found that zinc is distributed all along the dendrites while copper is mainly pinpointed within the spines. In spines, zinc content is higher within the spine head while copper is higher within the spine neck. Such specific distributions suggested metal interactions with cytoskeleton proteins. Zinc supplementation induced the increase of β-tubulin content in dendrites. Copper supplementation impaired the β-tubulin and F-actin networks. Copper chelation resulted in the decrease of F-actin content in dendrites, drastically reducing the number of F-actin protrusions. These results indicate that zinc is involved in microtubule stability whereas copper is essential for actin-dependent stability of dendritic spines, although copper excess can impair the dendritic cytoskeleton.

Active Site Mutations Change the Cleavage Specificity of Neprilysin

PubMed Central

Sexton, Travis; Hitchcook, Lisa J.; Rodgers, David W.; Bradley, Luke H.; Hersh, Louis B.

2012-01-01

Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe563 and Ser546. Among the mutants studied in detail we observed changes in their activity towards leucine5-enkephalin, insulin B chain, and amyloid β1–40. For example, NEPF563I displayed an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, while mutant NEPS546E was less discriminating than neprilysin. Mutants NEPF563L and NEPS546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß1–40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential. PMID:22384224

The Critical Roles of Zinc: Beyond Impact on Myocardial Signaling

PubMed Central

Lee, Sung Ryul; Noh, Su Jin; Pronto, Julius Ryan; Jeong, Yu Jeong; Kim, Hyoung Kyu; Song, In Sung; Xu, Zhelong; Kwon, Hyog Young; Kang, Se Chan; Sohn, Eun-Hwa; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari

2015-01-01

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+. PMID:26330751

Probing the effect of the non-active-site mutation Y229W in New Delhi metallo-β-lactamase-1 by site-directed mutagenesis, kinetic studies, and molecular dynamics simulations.

PubMed

Chen, Jiao; Chen, Hui; Shi, Yun; Hu, Feng; Lao, Xingzhen; Gao, Xiangdong; Zheng, Heng; Yao, Wenbing

2013-01-01

New Delhi metallo-β-lactamase-1 (NDM-1) has attracted extensive attention for its high catalytic activities of hydrolyzing almost all β-lactam antibiotics. NDM-1 shows relatively higher similarity to subclass B1 metallo-β-lactamases (MβLs), but its residue at position 229 is identical to that of B2/B3 MβLs, which is a Tyr instead of a B1-MβL-conserved Trp. To elucidate the possible role of Y229 in the bioactivity of NDM-1, we performed mutagenesis study and molecular dynamics (MD) simulations. Although residue Y229 is spatially distant from the active site and not contacting directly with the substrate or zinc ions, the Y229W mutant was found to have higher kcat and Km values than those of wild-type NDM-1, resulting in 1 ∼ 7 fold increases in k(cat) /K(m) values against tested antibiotics. In addition, our MD simulations illustrated the enhanced flexibility of Loop 2 upon Y229W mutation, which could increase the kinetics of both substrate entrance (kon) and product egress (koff). The enhanced flexibility of Loop 2 might allow the enzyme to adjust the geometry of its active site to accommodate substrates with different structures, broadening its substrate spectrum. This study indicated the possible role of the residue at position 229 in the evolution of NDM-1.

Kinetic modelling for zinc (II) ions biosorption onto Luffa cylindrica

NASA Astrophysics Data System (ADS)

Oboh, I.; Aluyor, E.; Audu, T.

2015-03-01

The biosorption of Zinc (II) ions onto a biomaterial - Luffa cylindrica has been studied. This biomaterial was characterized by elemental analysis, surface area, pore size distribution, scanning electron microscopy, and the biomaterial before and after sorption, was characterized by Fourier Transform Infra Red (FTIR) spectrometer. The kinetic nonlinear models fitted were Pseudo-first order, Pseudo-second order and Intra-particle diffusion. A comparison of non-linear regression method in selecting the kinetic model was made. Four error functions, namely coefficient of determination (R2), hybrid fractional error function (HYBRID), average relative error (ARE), and sum of the errors squared (ERRSQ), were used to predict the parameters of the kinetic models. The strength of this study is that a biomaterial with wide distribution particularly in the tropical world and which occurs as waste material could be put into effective utilization as a biosorbent to address a crucial environmental problem.

Unprecedented chemosensing behavior of novel tetra-substituted benzimidazole zinc(II) phthalocynine for selective detection of Bi3 + ion: Synthesis, characterization and ROS generation

NASA Astrophysics Data System (ADS)

Ullah, Azeem; Shah, Faheem; Khan, Imran; Anwar, Muhammad; Shah, Kiramat; Muhammad, Munira Taj; Ahmad, Farid

2018-03-01

In this work, synthesis of novel symmetrical 4-(2-bromo-4-(5-bromo-1H-benzo[d] imidazol-2-yl) phenoxy) tetra substituted zinc phthalocyanine has been reported. The novel benzimidazole zinc phthlocynine compound (3) has been characterized by MALDI-TOF MS, FT-IR, UV-vis, and 1H NMR spectroscopy. This new compound 3 displayed excellent selectivity towards Bi3 + ion in the presence of other competitive ions including Ca2 +, Cd2 +, Co2 + Cu2 +, Fe3 +, Hg2 +, Sn2 +, Mg2 +, Na+, Ni2 + and Pb2 + respectively. Upon addition of Bi3 + into the solution of compound 3 in DMSO, dramatic change was observed in the Q- and the B-bands in UV-visible spectra as a result of donor acceptor interactions. Reactive oxygen species (ROS) were also studied using 2,7-dichlorofluorescin diacetate (DCFH-DA) a fluorescent probe which is converted to highly fluorescent dichlorofluorescein (DCF) in the presence of ROS. This property of non-aggregating zinc phthalocyanine is promising as a photosensitizer in photodynamic therapy of cancer.

Properties of Zinc Oxide Nanoparticles and Their Activity Against Microbes

NASA Astrophysics Data System (ADS)

Siddiqi, Khwaja Salahuddin; ur Rahman, Aziz; Tajuddin; Husen, Azamal

2018-05-01

Zinc oxide is an essential ingredient of many enzymes, sun screens, and ointments for pain and itch relief. Its microcrystals are very efficient light absorbers in the UVA and UVB region of spectra due to wide bandgap. Impact of zinc oxide on biological functions depends on its morphology, particle size, exposure time, concentration, pH, and biocompatibility. They are more effective against microorganisms such as Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Sarcina lutea, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Pseudomonas vulgaris, Candida albicans, and Aspergillus niger. Mechanism of action has been ascribed to the activation of zinc oxide nanoparticles by light, which penetrate the bacterial cell wall via diffusion. It has been confirmed from SEM and TEM images of the bacterial cells that zinc oxide nanoparticles disintegrate the cell membrane and accumulate in the cytoplasm where they interact with biomolecules causing cell apoptosis leading to cell death.

Properties of Zinc Oxide Nanoparticles and Their Activity Against Microbes.

PubMed

Siddiqi, Khwaja Salahuddin; Ur Rahman, Aziz; Tajuddin; Husen, Azamal

2018-05-08

Zinc oxide is an essential ingredient of many enzymes, sun screens, and ointments for pain and itch relief. Its microcrystals are very efficient light absorbers in the UVA and UVB region of spectra due to wide bandgap. Impact of zinc oxide on biological functions depends on its morphology, particle size, exposure time, concentration, pH, and biocompatibility. They are more effective against microorganisms such as Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Sarcina lutea, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Pseudomonas vulgaris, Candida albicans, and Aspergillus niger. Mechanism of action has been ascribed to the activation of zinc oxide nanoparticles by light, which penetrate the bacterial cell wall via diffusion. It has been confirmed from SEM and TEM images of the bacterial cells that zinc oxide nanoparticles disintegrate the cell membrane and accumulate in the cytoplasm where they interact with biomolecules causing cell apoptosis leading to cell death.

Crystal structure of human S100A8 in complex with zinc and calcium.

PubMed

Lin, Haili; Andersen, Gregers Rom; Yatime, Laure

2016-06-01

S100 proteins are a large family of calcium binding proteins present only in vertebrates. They function intra- and extracellularly both as regulators of homeostatic processes and as potent effectors during inflammation. Among these, S100A8 and S100A9 are two major constituents of neutrophils that can assemble into homodimers, heterodimers and higher oligomeric species, including fibrillary structures found in the ageing prostate. Each of these forms assumes specific functions and their formation is dependent on divalent cations, notably calcium and zinc. In particular, zinc appears as a major regulator of S100 protein function in a disease context. Despite this central role, no structural information on how zinc bind to S100A8/S100A9 and regulates their quaternary structure is yet available. Here we report two crystallographic structures of calcium and zinc-loaded human S100A8. S100A8 binds two zinc ions per homodimer, through two symmetrical, all-His tetracoordination sites, revealing a classical His-Zn binding mode for the protein. Furthermore, the presence of a (Zn)2-cacodylate complex in our second crystal form induces ligand swapping within the canonical His4 zinc binding motif, thereby creating two new Zn-sites, one of which involves residues from symmetry-related molecules. Finally, we describe the calcium-induced S100A8 tetramer and reveal how zinc stabilizes this tetramer by tightening the dimer-dimer interface. Our structures of Zn(2+)/Ca(2+)-bound hS100A8 demonstrate that S100A8 is a genuine His-Zn S100 protein. Furthermore, they show how zinc stabilizes S100A8 tetramerization and potentially mediates the formation of novel interdimer interactions. We propose that these zinc-mediated interactions may serve as a basis for the generation of larger oligomers in vivo.

Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site.

PubMed

Roston, Daniel; Demapan, Darren; Cui, Qiang

2016-06-15

A reaction's transition state (TS) structure plays a critical role in determining reactivity and has important implications for the design of catalysts, drugs, and other applications. Here, we explore TS structure in the enzyme alkaline phosphatase using hybrid Quantum Mechanics/Molecular Mechanics simulations. We find that minor perturbations to the substrate have major effects on TS structure and the way the enzyme stabilizes the TS. Substrates with good leaving groups (LGs) have little cleavage of the phosphorus-LG bond at the TS, while substrates with poor LGs have substantial cleavage of that bond. The results predict nonlinear free energy relationships for a single rate-determining step, and substantial differences in kinetic isotope effects for different substrates; both trends were observed in previous experimental studies, although the original interpretations differed from the present model. Moreover, due to different degrees of phosphorus-LG bond cleavage at the TS for different substrates, the LG is stabilized by different interactions at the TS: while a poor LG is directly stabilized by an active site zinc ion, a good LG is mainly stabilized by active site water molecules. Our results demonstrate the considerable plasticity of TS structure and stabilization in enzymes. Furthermore, perturbations to reactivity that probe TS structure experimentally (i.e., substituent effects) may substantially perturb the TS they aim to probe, and thus classical experimental approaches such as free energy relations should be interpreted with care.

Fe(2+) substrate transport through ferritin protein cage ion channels influences enzyme activity and biomineralization.

PubMed

Behera, Rabindra K; Torres, Rodrigo; Tosha, Takehiko; Bradley, Justin M; Goulding, Celia W; Theil, Elizabeth C

2015-09-01

Ferritins, complex protein nanocages, form internal iron-oxy minerals (Fe2O3·H2O), by moving cytoplasmic Fe(2+) through intracage ion channels to cage-embedded enzyme (2Fe(2+)/O2 oxidoreductase) sites where ferritin biomineralization is initiated. The products of ferritin enzyme activity are diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino acid side chains of D127 from each of three cage subunits project into ferritin ion channels near the interior ion channel exits and, thus, could direct Fe(2+) movement to the internal enzyme sites. Ferritin D127E was designed and analyzed to probe properties of ion channel size and carboxylate crowding near the internal ion channel opening. Glu side chains are chemically equivalent to, but longer by one -CH2 than Asp, side chains. Ferritin D127E assembled into normal protein cages, but diferric peroxo formation (enzyme activity) was not observed, when measured at 650 nm (DFP λ max). The caged biomineral formation, measured at 350 nm in the middle of the broad, nonspecific Fe(3+)-O absorption band, was slower. Structural differences (protein X-ray crystallography), between ion channels in wild type and ferritin D127E, which correlate with the inhibition of ferritin D127E enzyme activity include: (1) narrower interior ion channel openings/pores; (2) increased numbers of ion channel protein-metal binding sites, and (3) a change in ion channel electrostatics due to carboxylate crowding. The contributions of ion channel size and structure to ferritin activity reflect metal ion transport in ion channels are precisely regulated both in ferritin protein nanocages and membranes of living cells.

Fe2+ Substrate Transport through Ferritin Protein Cage Ion Channels Influences Enzyme Activity and Biomineralization

PubMed Central

Behera, Rabindra K.; Torres, Rodrigo; Tosha, Takehiko; Bradley, Justin M.; Goulding, Celia W.; Theil, Elizabeth C.

2015-01-01

Ferritins, complex protein nanocages, form internal iron-oxy minerals (Fe2O3.H2O), by moving cytoplasmic Fe2+ through intracage ion channels to cage-embedded enzyme (2Fe2+/O2 oxidoreductase) sites where ferritin biomineralization is initiated. The products of ferritin enzyme activity are diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino acid side chains of D127 from each of three cage subunits project into ferritin ion channels near the interior ion channel exits and, thus, could direct Fe2+ movement to the internal enzyme sites. Ferritin D127E was designed and analyzed to probe properties of ion channel size and carboxylate crowding near the internal ion channel opening. Glu side chains are chemically equivalent to, but longer by one – CH2 than Asp, side chains. Ferritin D127E assembled into normal protein cages, but diferric peroxo formation (enzyme activity) was not observed, when measured at 650nm (DFP λmax). The caged biomineral formation, measured at 350 nm in the middle of the broad, nonspecific Fe3+-O absorption band, was slower. Structural differences (protein X-ray crystallography), between ion channels in wild type and ferritin D127E, which correlate with the inhibition of ferritin D127E enzyme activity include: 1. narrower interior ion channel openings/pores, 2. increased numbers of ion channel protein-metal binding sites, and 3. a change in ion channel electrostatics due to carboxylate crowding. The contributions of ion channel size and structure to ferritin activity reflect metal ion transport in ion channels are precisely regulated both in ferritin protein nanocages and membranes of living cells. PMID:26202907

Deep Sequencing of Random Mutant Libraries Reveals the Active Site of the Narrow Specificity CphA Metallo-β-Lactamase is Fragile to Mutations.

PubMed

Sun, Zhizeng; Mehta, Shrenik C; Adamski, Carolyn J; Gibbs, Richard A; Palzkill, Timothy

2016-09-12

CphA is a Zn(2+)-dependent metallo-β-lactamase that efficiently hydrolyzes only carbapenem antibiotics. To understand the sequence requirements for CphA function, single codon random mutant libraries were constructed for residues in and near the active site and mutants were selected for E. coli growth on increasing concentrations of imipenem, a carbapenem antibiotic. At high concentrations of imipenem that select for phenotypically wild-type mutants, the active-site residues exhibit stringent sequence requirements in that nearly all residues in positions that contact zinc, the substrate, or the catalytic water do not tolerate amino acid substitutions. In addition, at high imipenem concentrations a number of residues that do not directly contact zinc or substrate are also essential and do not tolerate substitutions. Biochemical analysis confirmed that amino acid substitutions at essential positions decreased the stability or catalytic activity of the CphA enzyme. Therefore, the CphA active - site is fragile to substitutions, suggesting active-site residues are optimized for imipenem hydrolysis. These results also suggest that resistance to inhibitors targeted to the CphA active site would be slow to develop because of the strong sequence constraints on function.

Zinc in human health: effect of zinc on immune cells.

PubMed

Prasad, Ananda S

2008-01-01

Although the essentiality of zinc for plants and animals has been known for many decades, the essentiality of zinc for humans was recognized only 40 years ago in the Middle East. The zinc-deficient patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in an experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, hyperammonemia, neurosensory disorders, and decreased lean body mass. It appears that zinc deficiency is prevalent in the developing world and as many as two billion subjects may be growth retarded due to zinc deficiency. Besides growth retardation and immune dysfunctions, cognitive impairment due to zinc deficiency also has been reported recently. Our studies in the cell culture models showed that the activation of many zinc-dependent enzymes and transcription factors were adversely affected due to zinc deficiency. In HUT-78 (T helper 0 [Th(0)] cell line), we showed that a decrease in gene expression of interleukin-2 (IL-2) and IL-2 receptor alpha(IL-2Ralpha) were due to decreased activation of nuclear factor-kappaB (NF-kappaB) in zinc deficient cells. Decreased NF-kappaB activation in HUT-78 due to zinc deficiency was due to decreased binding of NF-kappaB to DNA, decreased level of NF-kappaB p105 (the precursor of NF-kappaB p50) mRNA, decreased kappaB inhibitory protein (IkappaB) phosphorylation, and decreased Ikappa kappa. These effects of zinc were cell specific. Zinc also is an antioxidant and has anti-inflammatory actions. The therapeutic roles of zinc in acute infantile diarrhea, acrodermatitis enteropathica, prevention of blindness in patients with age-related macular degeneration, and treatment of common cold with zinc have been reported. In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Que, Emily L.; Duncan, Francesca E.; Bayer, Amanda R.

During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as ‘zinc sparks.’ The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as ‘hardening’, which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. Using x-ray fluorescence microscopy,more » transmission and scanning electron microscopy, and biological function assays, we tested the hypothesis that zinc release contributes to ZP hardening. We found that the zinc content in the ZP increases by 300% following activation and that zinc exposure modulates the architecture of the ZP matrix. Importantly, zinc-induced structural changes of the ZP have a direct biological consequence; namely, they reduce the ability of sperm to bind to the ZP. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. Finally, this adds a previously unrecognized factor, namely zinc, to the process of ZP hardening.« less

Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy

DOE PAGES

Que, Emily L.; Duncan, Francesca E.; Bayer, Amanda R.; ...

2017-01-19

During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as ‘zinc sparks.’ The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as ‘hardening’, which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. Using x-ray fluorescence microscopy,more » transmission and scanning electron microscopy, and biological function assays, we tested the hypothesis that zinc release contributes to ZP hardening. We found that the zinc content in the ZP increases by 300% following activation and that zinc exposure modulates the architecture of the ZP matrix. Importantly, zinc-induced structural changes of the ZP have a direct biological consequence; namely, they reduce the ability of sperm to bind to the ZP. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. Finally, this adds a previously unrecognized factor, namely zinc, to the process of ZP hardening.« less

Insights into Substrate Specificity and Metal Activation of Mammalian Tetrahedral Aspartyl Aminopeptidase*

PubMed Central

Chen, Yuanyuan; Farquhar, Erik R.; Chance, Mark R.; Palczewski, Krzysztof; Kiser, Philip D.

2012-01-01

Aminopeptidases are key enzymes involved in the regulation of signaling peptide activity. Here, we present a detailed biochemical and structural analysis of an evolutionary highly conserved aspartyl aminopeptidase called DNPEP. We show that this peptidase can cleave multiple physiologically relevant substrates, including angiotensins, and thus may play a key role in regulating neuron function. Using a combination of x-ray crystallography, x-ray absorption spectroscopy, and single particle electron microscopy analysis, we provide the first detailed structural analysis of DNPEP. We show that this enzyme possesses a binuclear zinc-active site in which one of the zinc ions is readily exchangeable with other divalent cations such as manganese, which strongly stimulates the enzymatic activity of the protein. The plasticity of this metal-binding site suggests a mechanism for regulation of DNPEP activity. We also demonstrate that DNPEP assembles into a functionally relevant tetrahedral complex that restricts access of peptide substrates to the active site. These structural data allow rationalization of the enzyme's preference for short peptide substrates with N-terminal acidic residues. This study provides a structural basis for understanding the physiology and bioinorganic chemistry of DNPEP and other M18 family aminopeptidases. PMID:22356908

Structural changes at the metal ion binding site during the phosphoglucomutase reaction.

PubMed

Ray, W J; Post, C B; Liu, Y; Rhyu, G I

1993-01-12

An electron density map of the reactive, Cd2+ form of crystalline phosphoglucomutase from X-ray diffraction studies shows that the enzymic phosphate donates a nonbridging oxygen to the ligand sphere of the bound metal ion, which appears to be tetracoordinate. 31P and 113Cd NMR spectroscopy are used to assess changes in the properties of bound Cd2+ produced by substrate/product and by substrate/product analog inhibitors. The approximately 50 ppm downfield shift of the 113Cd resonance on formation of the complex of dephosphoenzyme and glucose 1,6-bisphosphate is associated with the initial sugar-phosphate binding step and likely involves a change in the geometry of the coordinating ligands. This interpretation is supported by spectral studies involving various complexes of the active Co2+ and Ni(2+)-enzyme. In addition, there is a loss of the 31P-113Cd J coupling that characterizes the monophosphate complexes of the Cd2+ enzyme either during or immediately after the PO3- transfer step that produces the bisphosphate complex, indicating a further change at the metal binding site. The implications of these observations with respect to the PO3- transfer process in the phosphoglucomutase reaction are considered. The apparent plasticity of the ligand sphere of the active site metal ion in this system may allow a single metal ion to act as a chaperone for a nonbridging oxygen during PO3- transfer or to allow a change in metal ion coordination during catalysis. A general NMR line shape/chemical-exchange analysis for evaluating binding in protein-ligand systems when exchange is intermediate to fast on the NMR time scale is described. Its application to the present system involves multiple exchange sites that depend on a single binding rate, thereby adding further constraints to the analysis.

Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel.

PubMed

Silverman, William R; Bannister, John P A; Papazian, Diane M

2004-11-01

In ether-a-go-go K+ channels, voltage-dependent activation is modulated by ion binding to a site located in an extracellular-facing crevice between transmembrane segments S2 and S3 in the voltage sensor. We find that acidic residues D278 in S2 and D327 in S3 are able to coordinate a variety of divalent cations, including Mg2+, Mn2+, and Ni2+, which have qualitatively similar functional effects, but different half-maximal effective concentrations. Our data indicate that ions binding to individual voltage sensors in the tetrameric channel act without cooperativity to modulate activation gating. We have taken advantage of the unique phenotype of Ni2+ in the D274A channel, which contains a mutation of a nonbinding site residue, to demonstrate that ions can access the binding site from the extracellular solution when the voltage sensor is in the resting conformation. Our results are difficult to reconcile with the x-ray structure of the KvAP K+ channel, in which the binding site residues are widely separated, and with the hydrophobic paddle model for voltage-dependent activation, in which the voltage sensor domain, including the S3-S4 loop, is near the cytoplasmic side of the membrane in the closed channel.

Human HDAC7 Harbors a Class IIa Histone Deacetylase-specific Zinc Binding Motif and Cryptic Deacetylase Activity*S⃞

PubMed Central

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P.; Lewis, Timothy A.; Maglathin, Rebecca L.; McLean, Thomas H.; Bochkarev, Alexey; Plotnikov, Alexander N.; Vedadi, Masoud; Arrowsmith, Cheryl H.

2008-01-01

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators. PMID:18285338

Rational Design Synthesis and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases

DOE Office of Scientific and Technical Information (OSTI.GOV)

R Daher; M Coincon; M Fonvielle

2011-12-31

We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows Ki against class II Fbas from various pathogens in the nM range, with very highmore » selectivity (up to 105). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.« less

Binding of iron, zinc, and lead ions from aqueous solution by shea butter (Butyrospermun Parkii) seed husks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eromosele, I.C.; Otitolaye, O.O.

1994-08-01

Several workers have reported on the potential use of agricultural products as substrates for the removal of metal ions from aqueous solutions. These studies demonstrated that considerable amounts of metal ions can be removed from aqueous solutions by cellulosic materials. The merit in the use of the latter is their relative abundance and cheapness compared to conventional materials for the removal of toxic metal ions from waste-waters. In some of the studies, chemical modification of cellulosic materials significantly enhanced their ion-binding properties, providing greater flexibility in their applications to a wide range of heavy metal ions. Shea butter plant (Butyrospermunmore » Parkii) normally grows in the wild within the guinea-savana zone of Nigeria. The seeds are a rich source of edible oils and the husks are usually discarded. The husk is thus available in abundance and, hence, there is reason to examine its ion-binding properties for its possible application in the removal of toxic metal ions from industrial waste-waters. This paper reports on preliminary studies of the sorption of iron, zinc and lead ions from aqueous solution by modified and unmodified shea butter seed husks. 8 refs., 5 figs., 1 tab.« less

Zinc oxide nanorod clusters deposited seaweed cellulose sheet for antimicrobial activity.

PubMed

Bhutiya, Priyank L; Mahajan, Mayur S; Abdul Rasheed, M; Pandey, Manoj; Zaheer Hasan, S; Misra, Nirendra

2018-06-01

Seaweed cellulose was isolated from green seaweed Ulva fasciata using a common bleaching agent. Sheet containing porous mesh was prepared from the extracted seaweed crystalline cellulose along with zinc oxide (ZnO) nanorod clusters grown over the sheet by single step hydrothermal method. Seaweed cellulose and zinc oxide nanorod clusters deposited seaweed cellulose sheet was characterized by FT-IR, XRD, TGA, and SEM-EDX. Morphology showed that the diameter of zinc oxide nanorods were around 70nm. Zinc oxide nanorod clusters deposited on seaweed cellulose sheet gave remarkable antibacterial activity towards gram-positive (Staphylococcus aureus, Bacillus ceresus, Streptococcus thermophilis) and gram-negative (Escherichia coli, Pseudomonas aeruginous) microbes. Such deposited sheet has potential applications in pharmaceutical, biomedical, food packaging, water treatment and biotechnological industries. Copyright © 2018 Elsevier B.V. All rights reserved.

Synergistic cytotoxic effects of ions released by zinc-aluminum bronze and the metallic salts on osteoblastic cells.

PubMed

Grillo, Claudia A; Morales, María L; Mirífico, María V; Fernández Lorenzo de Mele, Mónica A

2013-07-01

The use of copper-based alloys for fixed dental crowns and bridges is increasingly widespread in several countries. The aim of this work is to study the dissolution of a zinc-aluminum-bronze and the cytotoxic effects of the ions released on UMR-106 osteoblastic cell line. Two sources of ions were used: (1) ions released by the metal alloy immersed in the cell culture and (2) salts of the metal ions. Conventional electrochemical techniques, atomic absorption spectroscopy [to obtain the average concentration of ions (AC) in solution], and energy dispersive X-ray (EDX) spectroscopy analysis were used to study the corrosion process. Corrosion tests revealed a strong influence of the composition of the electrolyte medium and the immersion time on the electrochemical response. The cytotoxicity was evaluated with (a) individual ions, (b) combinations of two ions, and (c) the mixture of all the ions released by a metal disc of the alloy. Importantly, synergistic cytotoxic effects were found when Al-Zn ion combinations were used at concentration levels lower than the cytotoxic threshold values of the individual ions. Cytotoxic effects in cells in the vicinity of the metal disc were also found. These results were interpreted considering synergistic effects and a diffusion controlled mechanism that yields to concentration levels, in the metal surroundings, several times higher than the measured AC value. Copyright © 2013 Wiley Periodicals, Inc.

Biomarkers of Nutrition for Development (BOND)—Zinc Review12345

PubMed Central

King, Janet C; Brown, Kenneth H; Gibson, Rosalind S; Krebs, Nancy F; Lowe, Nicola M; Siekmann, Jonathan H; Raiten, Daniel J

2016-01-01

Zinc is required for multiple metabolic processes as a structural, regulatory, or catalytic ion. Cellular, tissue, and whole-body zinc homeostasis is tightly controlled to sustain metabolic functions over a wide range of zinc intakes, making it difficult to assess zinc insufficiency or excess. The BOND (Biomarkers of Nutrition for Development) Zinc Expert Panel recommends 3 measurements for estimating zinc status: dietary zinc intake, plasma zinc concentration (PZC), and height-for-age of growing infants and children. The amount of dietary zinc potentially available for absorption, which requires an estimate of dietary zinc and phytate, can be used to identify individuals and populations at risk of zinc deficiency. PZCs respond to severe dietary zinc restriction and to zinc supplementation; they also change with shifts in whole-body zinc balance and clinical signs of zinc deficiency. PZC cutoffs are available to identify individuals and populations at risk of zinc deficiency. However, there are limitations in using the PZC to assess zinc status. PZCs respond less to additional zinc provided in food than to a supplement administered between meals, there is considerable interindividual variability in PZCs with changes in dietary zinc, and PZCs are influenced by recent meal consumption, the time of day, inflammation, and certain drugs and hormones. Insufficient data are available on hair, urinary, nail, and blood cell zinc responses to changes in dietary zinc to recommend these biomarkers for assessing zinc status. Of the potential functional indicators of zinc, growth is the only one that is recommended. Because pharmacologic zinc doses are unlikely to enhance growth, a growth response to supplemental zinc is interpreted as indicating pre-existing zinc deficiency. Other functional indicators reviewed but not recommended for assessing zinc nutrition in clinical or field settings because of insufficient information are the activity or amounts of zinc-dependent enzymes

[Influence of trematode invasion and zinc ions on the histometric peculiarities of haemocytes and some hematological indices of Planorbarius purpura (Gastropoda: Pulmonata: Bulinidae)].

PubMed

Kirichuk, G E; Stadnichenko, A P

2010-01-01

Cellular components of the Planorbarius purpura hemolymph are represented by three phyla of haemocytes (prohemocytes, eosinophilis microgranulocytes, and basophilis granulocytes) and vesicular cells. As a result of the invasions of P. purpura with the trematode Echinoparyphium aconiatum, changes of the linear dimensions of granular hemocytes and their nuclei took place. Moreover, an increase of the hemocytes' number per l mm3 of hemolymph and change of the percentages of different hemocyte types were recorded. Under the influence of zinc ions, linear dimensions of prohemocytes and their nuclei (at 10 MPCns of the toxicant) were changed. In granular hemocytes and abnormalities of all histometrical and hematological parameters were observed. All cytometrical, karyometrical, and hematological alterations were expressed more clearly in infested mollusks than in non-infested ones, and occurred usually under lower concentrations of zinc ions.

Removal of some metal ions by activated carbon prepared from Phaseolus aureus hulls.

PubMed

Rao, M Madhava; Ramana, D K; Seshaiah, K; Wang, M C; Chien, S W Chang

2009-07-30

Removal of lead [Pb(II)], zinc [Zn(II)], copper [Cu(II)], and cadmium [Cd(II)] from aqueous solutions using activated carbon prepared from Phaseolus aureus hulls (ACPAH), an agricultural waste was studied. The influence of various parameters such as effect of pH, contact time, adsorbent dose, and initial concentration of metal ions on the removal was evaluated by batch method. The removal of metal ions by ACPAH was pH dependent and the optimum pH values were 7.0, 8.0, 7.0 and 6.0 for Cu(II), Cd(II), Zn(II), and Pb(II), respectively. The sorption isotherms were studied using Langmuir, Freundlich, Dubinin-Radushkevich (D-R), and Temkin isotherm models. The maximum adsorption capacity values of ACPAH for metal ions were 21.8 mg g(-1) for Pb(II), 21.2 mg g(-1) for Zn(II), 19.5 mg g(-1) for Cu(II), and 15.7 mg g(-1) for Cd(II). The experiments demonstrated that the removal of metal ions followed the pseudo-second-order kinetic model. Desorption experiments were carried out using HCl solution with a view to regenerate the spent adsorbent and to recover the adsorbed metal ions.

Efficient and surface site-selective ion desorption by positron annihilation.

PubMed

Tachibana, Takayuki; Yamashita, Takashi; Nagira, Masaru; Yabuki, Hisakuni; Nagashima, Yasuyuki

2018-05-08

We compared positron- and electron-stimulated desorption (e + SD and ESD) of positive ions from a TiO 2 (110) surface. Although desorption of O + ions was observed in both experiments, the desorption efficiency caused by positron bombardment was larger by one order of magnitude than that caused by electron bombardment at an incident energy of 500 eV. e + SD of O + ions remained highly efficient with incident positron energies between 10 eV and 600 eV. The results indicate that e + SD of O + ions is predominantly caused by pair annihilation of surface-trapped positrons with inner-shell electrons. We also tested e + SD from water chemisorbed on the TiO 2 surface and found that the desorption of specific ions was enhanced by positron annihilation, above the ion yield with electron bombardment. This finding corroborates our conclusion that annihilation-site selectivity of positrons results in site-selective ion desorption from a bombarded surface.

Kinetic modelling for zinc (II) ions biosorption onto Luffa cylindrica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oboh, I., E-mail: innocentoboh@uniuyo.edu.ng; Aluyor, E.; Audu, T.

The biosorption of Zinc (II) ions onto a biomaterial - Luffa cylindrica has been studied. This biomaterial was characterized by elemental analysis, surface area, pore size distribution, scanning electron microscopy, and the biomaterial before and after sorption, was characterized by Fourier Transform Infra Red (FTIR) spectrometer. The kinetic nonlinear models fitted were Pseudo-first order, Pseudo-second order and Intra-particle diffusion. A comparison of non-linear regression method in selecting the kinetic model was made. Four error functions, namely coefficient of determination (R{sup 2}), hybrid fractional error function (HYBRID), average relative error (ARE), and sum of the errors squared (ERRSQ), were used tomore » predict the parameters of the kinetic models. The strength of this study is that a biomaterial with wide distribution particularly in the tropical world and which occurs as waste material could be put into effective utilization as a biosorbent to address a crucial environmental problem.« less

Two short basic sequences surrounding the zinc finger of nucleocapsid protein NCp10 of Moloney murine leukemia virus are critical for RNA annealing activity.

PubMed

De Rocquigny, H; Ficheux, D; Gabus, C; Allain, B; Fournie-Zaluski, M C; Darlix, J L; Roques, B P

1993-02-25

The 56 amino acid nucleocapsid protein (NCp10) of Moloney Murine Leukemia Virus, contains a CysX2CysX4HisX4Cys zinc finger flanked by basic residues. In vitro NCp10 promotes genomic RNA dimerization, a process most probably linked to genomic RNA packaging, and replication primer tRNA(Pro) annealing to the initiation site of reverse transcription. To characterize the amino-acid sequences involved in the various functions of NCp10, we have synthesized by solid phase method the native protein and a series of derived peptides shortened at the N- or C-terminus with or without the zinc finger domain. In the latter case, the two parts of the protein were linked by a Glycine - Glycine spacer. The in vitro studies of these peptides show that nucleic acid annealing activities of NCp10 do not require a zinc finger but are critically dependent on the presence of specific sequences located on each side of the CCHC domain and containing proline and basic residues. Thus, deletion of 11R or 49PRPQT, of the fully active 29 residue peptide 11RQGGERRRSQLDRDGGKKPRGPRGPRPQT53 leads to a complete loss of NCp10 activity. Therefore it is proposed that in NCp10, the zinc finger directs the spatial recognition of the target RNAs by the basic domains surrounding the zinc finger.

Two short basic sequences surrounding the zinc finger of nucleocapsid protein NCp10 of Moloney murine leukemia virus are critical for RNA annealing activity.

PubMed Central

De Rocquigny, H; Ficheux, D; Gabus, C; Allain, B; Fournie-Zaluski, M C; Darlix, J L; Roques, B P

1993-01-01

The 56 amino acid nucleocapsid protein (NCp10) of Moloney Murine Leukemia Virus, contains a CysX2CysX4HisX4Cys zinc finger flanked by basic residues. In vitro NCp10 promotes genomic RNA dimerization, a process most probably linked to genomic RNA packaging, and replication primer tRNA(Pro) annealing to the initiation site of reverse transcription. To characterize the amino-acid sequences involved in the various functions of NCp10, we have synthesized by solid phase method the native protein and a series of derived peptides shortened at the N- or C-terminus with or without the zinc finger domain. In the latter case, the two parts of the protein were linked by a Glycine - Glycine spacer. The in vitro studies of these peptides show that nucleic acid annealing activities of NCp10 do not require a zinc finger but are critically dependent on the presence of specific sequences located on each side of the CCHC domain and containing proline and basic residues. Thus, deletion of 11R or 49PRPQT, of the fully active 29 residue peptide 11RQGGERRRSQLDRDGGKKPRGPRGPRPQT53 leads to a complete loss of NCp10 activity. Therefore it is proposed that in NCp10, the zinc finger directs the spatial recognition of the target RNAs by the basic domains surrounding the zinc finger. Images PMID:8451185

Active-site monovalent cations revealed in a 1.55-Å-resolution hammerhead ribozyme structure.

PubMed

Anderson, Michael; Schultz, Eric P; Martick, Monika; Scott, William G

2013-10-23

We have obtained a 1.55-Å crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni under conditions that permit detailed observations of Na(+) ion binding in the ribozyme's active site. At least two such Na(+) ions are observed. The first Na(+) ion binds to the N7 of G10.1 and the adjacent A9 phosphate in a manner identical with that previously observed for divalent cations. A second Na(+) ion binds to the Hoogsteen face of G12, the general base in the hammerhead cleavage reaction, thereby potentially dissipating the negative charge of the catalytically active enolate form of the nucleotide base. A potential but more ambiguous third site bridges the A9 and scissile phosphates in a manner consistent with that of previous predictions. Hammerhead ribozymes have been observed to be active in the presence of high concentrations of monovalent cations, including Na(+), but the mechanism by which monovalent cations substitute for divalent cations in hammerhead catalysis remains unclear. Our results enable us to suggest that Na(+) directly and specifically substitutes for divalent cations in the hammerhead active site. The detailed geometry of the pre-catalytic active-site complex is also revealed with a new level of precision, thanks to the quality of the electron density maps obtained from what is currently the highest-resolution ribozyme structure in the Protein Data Bank. Copyright © 2013 Elsevier Ltd. All rights reserved.

Zinc cobalt sulfide nanosheets array derived from 2D bimetallic metal-organic frameworks for high-performance supercapacitor.

PubMed

Tao, Kai; Han, Xue; Cheng, Qiuhui; Yang, Yujing; Yang, Zheng; Ma, Qingxiang; Han, Lei

2018-04-19

Porous ternary metal sulfide integrated electrode materials with abundant electroactive sites and redox reactions are very promising for supercapacitors. Here, porous zinc cobalt sulfide nanosheets array on Ni foam (Zn-Co-S/NF) has been successfully constructed by a facile growth of 2D bimetallic zinc/cobalt-based metal-organic frameworks (Zn/Co-MOF) nanosheets with leaf-like morphology on Ni foam, followed by additional sulfurization. The Zn-Co-S/NF nanosheets array is directly acted as an electrode for supercapacitor, showing much better electrochemical performance (2354.3 F g-1 and 88.6% retention over 1000 cycles) when compared with zinc cobalt sulfide powder (355.3 F g-1 and 75.8% retention over 1000 cycles), which is originated from good electric conductivity and mechanical stability, abundant electroactive sites, and facilitated transportation of electron and electrolyte ion endowed by the unique nanosheets array structure. The asymmetric supercapacitor (ASC) device assembled from Zn-Co-S/NF and activated carbon electrodes can deliver the highest energy density of 31.9 Wh kg-1 and the maximum power density of 8.5 kW kg-1. Most importantly, this ASC also presents good cycling stability (97% retention over 1000 cycles). Furthermore, a red light-emitting diode (LED) can be illuminated by two connected ASCs, indicating that as-synthesized Zn-Co-S/NF hold great potential for practical applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and characterization of zinc chloride containing poly(acrylic acid) hydrogel by gamma irradiation

NASA Astrophysics Data System (ADS)

Park, Jong-Seok; Kuang, Jia; Gwon, Hui-Jeong; Lim, Youn-Mook; Jeong, Sung-In; Shin, Young-Min; Seob Khil, Myung; Nho, Young-Chang

2013-07-01

In this study, the characterization of zinc chloride incorporated into a poly(acrylic acid) (PAAc) hydrogel prepared by gamma-ray irradiation was investigated. Zinc chloride powder with different concentrations was dissolved in the PAAc solution, and it was crosslinked with gamma-ray irradiation. The effects of various parameters such as zinc ion concentration and irradiation doses on characteristics of the hydrogel formed were investigated in detail for obtaining an antibacterial wound dressing. In addition, the gel content, pH-sensitive (pH 4 or 7) swelling ratio, and UV-vis absorption spectra of the zinc particles in the hydrogels were characterized. Moreover, antibacterial properties of these new materials against Staphylococcus aureus and Escherichia coli strains were observed on solid growth media. The antibacterial tests indicated that the zinc chloride containing PAAc hydrogels have good antibacterial activity.

Formulation and Evaluation of Antibacterial Creams and Gels Containing Metal Ions for Topical Application

PubMed Central

Chen, Mei X.; Alexander, Kenneth S.

2016-01-01

Background. Skin infections occur commonly and often present therapeutic challenges to practitioners due to the growing concerns regarding multidrug-resistant bacterial, viral, and fungal strains. The antimicrobial properties of zinc sulfate and copper sulfate are well known and have been investigated for many years. However, the synergistic activity between these two metal ions as antimicrobial ingredients has not been evaluated in topical formulations. Objective. The aims of the present study were to (1) formulate topical creams and gels containing zinc and copper alone or in combination and (2) evaluate the in vitro antibacterial activity of these metal ions in the formulations. Method. Formulation of the gels and creams was followed by evaluating their organoleptic characteristics, physicochemical properties, and in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. Results. Zinc sulfate and copper sulfate had a strong synergistic antibacterial activity in the creams and gels. The minimum effective concentration was found to be 3 w/w% for both active ingredients against the two tested microorganisms. Conclusions. This study evaluated and confirmed the synergistic in vitro antibacterial effect of copper sulfate and zinc sulfate in a cream and two gels. PMID:27885352

[Synergistic application of zinc and vitamin C to support memory, attention and the reduction of the risk of the neurological diseases].

PubMed

Gromova, O A; Torshin, I Yu; Pronin, A V; Kilchevsky, M A

Zinc and vitamin C supplementation of the body is important for CNS functioning. Zinc ions are involved in the neurotransmission (signal transmission from acetylcholine, catecholamine, serotonin, prostaglandin receptors) and in ubiquitin-related protein degradation. Zinc deficits are associated with Alzheimer's disease and depression. Zinc supplementation (10-30 mg daily) improves neurologic recovery rate in patients with stroke and brain injury, has a positive impact on memory and reduces hyperactivity in children. Vitamin C, a zinc synergist, maintains antioxidant resources of the brain, synaptic activity and detoxification. Vitamin C in dose 130-500 mg daily should be used to prevent dementia and neurodegenerative pathology.

Irradiation of zinc single crystal with 500 keV singly-charged carbon ions: surface morphology, structure, hardness, and chemical modifications

NASA Astrophysics Data System (ADS)

Waqas Khaliq, M.; Butt, M. Z.; Saleem, Murtaza

2017-07-01

Cylindrical specimens of (1 0 4) oriented zinc single crystal (diameter  =  6 mm and length  =  5 mm) were irradiated with 500 keV C+1 ions with the help of a Pelletron accelerator. Six specimens were irradiated in an ultra-high vacuum (~10‒8 Torr) with different ion doses, namely 3.94  ×  1014, 3.24  ×  1015, 5.33  ×  1015, 7.52  ×  1015, 1.06  ×  1016, and 1.30  ×  1016 ions cm-2. A field emission scanning electron microscope (FESEM) was utilized for the morphological study of the irradiated specimens. Formation of nano- and sub-micron size rods, clusters, flower- and fork-like structures, etc, was observed. Surface roughness of the irradiated specimens showed an increasing trend with the ions dose. Energy dispersive x-ray spectroscopy (EDX) helped to determine chemical modifications in the specimens. It was found that carbon content varied in the range 22.86-31.20 wt.% and that oxygen content was almost constant, with an average value of 10.16 wt.%. The balance content was zinc. Structural parameters, i.e. crystallite size and lattice strain, were determined by Williamson-Hall analysis using x-ray diffraction (XRD) patterns of the irradiated specimens. Both crystallite size and lattice strain showed a decreasing trend with the increasing ions dose. A good linear relationship between crystallite size and lattice strain was observed. Surface hardness depicted a decreasing trend with the ions dose and followed an inverse Hall-Petch relation. FTIR spectra of the specimens revealed that absorption bands gradually diminish as the dose of singly-charged carbon ions is increased from 3.94  ×  1014 ions cm-1 to 1.30  ×  1016 ions cm-1. This indicates progressive deterioration of chemical bonds with the increase in ion dose.

Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site

PubMed Central

Stafford, Kate A.; Palmer III, Arthur G.

2014-01-01

Ribonuclease H1 (RNase H) enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. In this work, we describe molecular dynamics simulations of the E. coli homolog in complex with magnesium ions, as well as simulations of other homologs in their apo states. Collectively, these results suggest that the active site is highly rigid in the apo state of all homologs studied and is conformationally preorganized to favor the binding of a magnesium ion. Notably, representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit similar active-site rigidity, suggesting that this dynamic feature is only subtly modulated by amino acid sequence and is primarily imposed by the distinctive RNase H protein fold. PMID:25075292

Catalytically active nanorotor reversibly self-assembled by chemical signaling within an eight-component network.

PubMed

Goswami, Abir; Pramanik, Susnata; Schmittel, Michael

2018-04-17

A catalytically active three-component nanorotor is reversibly self-assembled and disassembled by remote control. When zinc(ii) ions (2 equiv.) are added as an external chemical trigger to the mixture of transmitter [Cu(1)]+ and pre-rotor assembly [(S)·(R)], two equiv. of copper(i) ions translocate from [Cu(1)]+ to the two phenanthroline sites of [(S)·(R)]. As a result, [Zn(1)]2+ forms along with the three-component assembly [Cu2(S)(R)]2+, which is both a nanorotor (k298 = 46 kHz, ΔH‡ = 49.1 ± 0.4 kJ mol-1, ΔS‡ = 9.5 ± 1.7 J mol-1 K-1) and a catalyst for click reactions (catalysis ON: A + B→AB). Removal of zinc from the mixture reverts the translocation sequence and thus commands disassembly of the catalytically active rotor (catalysis OFF). The ON/OFF catalytic cycle was run twice in situ in the full network.

Ionizable Side Chains at Catalytic Active Sites of Enzymes

PubMed Central

Jimenez-Morales, David; Liang, Jie

2012-01-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1072 Å3. The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes. PMID:22484856

Ion beam sputter deposited zinc telluride films

NASA Technical Reports Server (NTRS)

Gulino, D. A.

1986-01-01

Zinc telluride is of interest as a potential electronic device material, particularly as one component in an amorphous superlattice, which is a new class of interesting and potentially useful materials. Some structural and electronic properties of ZnTe films deposited by argon ion beam sputter deposition are described. Films (up to 3000 angstroms thick) were deposited from a ZnTe target. A beam energy of 1000 eV and a current density of 4 mA/sq cm resulted in deposition rates of approximately 70 angstroms/min. The optical band gap was found to be approximately 1.1 eV, indicating an amorphous structure, as compared to a literature value of 2.26 eV for crystalline material. Intrinsic stress measurements showed a thickness dependence, varying from tensile for thicknesses below 850 angstroms to compressive for larger thicknesses. Room temperature conductivity measurement also showed a thickness dependence, with values ranging from 1.86 x 10 to the -6th/ohm cm for 300 angstrom film to 2.56 x 10 to the -1/ohm cm for a 2600 angstrom film. Measurement of the temperature dependence of the conductivity for these films showed complicated behavior which was thickness dependent. Thinner films showed at least two distinct temperature dependent conductivity mechanisms, as described by a Mott-type model. Thicker films showed only one principal conductivity mechanism, similar to what might be expected for a material with more crystalline character.

Ion beam sputter deposited zinc telluride films

NASA Technical Reports Server (NTRS)

Gulino, D. A.

1985-01-01

Zinc telluride is of interest as a potential electronic device material, particularly as one component in an amorphous superlattice, which is a new class of interesting and potentially useful materials. Some structural and electronic properties of ZnTe films deposited by argon ion beam sputter depoairion are described. Films (up to 3000 angstroms thick) were deposited from a ZnTe target. A beam energy of 1000 eV and a current density of 4 mA/sq. cm. resulted in deposition rates of approximately 70 angstroms/min. The optical band gap was found to be approximately 1.1 eV, indicating an amorphous structure, as compared to a literature value of 2.26 eV for crystalline material. Intrinsic stress measurements showed a thickness dependence, varying from tensile for thicknesses below 850 angstroms to compressive for larger thicknesses. Room temperature conductivity measurement also showed a thickness dependence, with values ranging from 1.86 x to to the -6/ohm. cm. for 300 angstrom film to 2.56 x 10 to the -1/ohm. cm. for a 2600 angstrom film. Measurement of the temperature dependence of the conductivity for these films showed complicated behavior which was thickness dependent. Thinner films showed at least two distinct temperature dependent conductivity mechanisms, as described by a Mott-type model. Thicker films showed only one principal conductivity mechanism, similar to what might be expected for a material with more crystalline character.

Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes

PubMed Central

Maret, Wolfgang

2017-01-01

About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic β- and α-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the patho-biochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of β-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions. PMID:28401081

Selectivity of externally facing ion-binding sites in the Na/K pump to alkali metals and organic cations

PubMed Central

Ratheal, Ian M.; Virgin, Gail K.; Yu, Haibo; Roux, Benoît; Gatto, Craig; Artigas, Pablo

2010-01-01

The Na/K pump is a P-type ATPase that exchanges three intracellular Na+ ions for two extracellular K+ ions through the plasmalemma of nearly all animal cells. The mechanisms involved in cation selection by the pump's ion-binding sites (site I and site II bind either Na+ or K+; site III binds only Na+) are poorly understood. We studied cation selectivity by outward-facing sites (high K+ affinity) of Na/K pumps expressed in Xenopus oocytes, under voltage clamp. Guanidinium+, methylguanidinium+, and aminoguanidinium+ produced two phenomena possibly reflecting actions at site III: (i) voltage-dependent inhibition (VDI) of outwardly directed pump current at saturating K+, and (ii) induction of pump-mediated, guanidinium-derivative–carried inward current at negative potentials without Na+ and K+. In contrast, formamidinium+ and acetamidinium+ induced K+-like outward currents. Measurement of ouabain-sensitive ATPase activity and radiolabeled cation uptake confirmed that these cations are external K+ congeners. Molecular dynamics simulations indicate that bound organic cations induce minor distortion of the binding sites. Among tested metals, only Li+ induced Na+-like VDI, whereas all metals tested except Na+ induced K+-like outward currents. Pump-mediated K+-like organic cation transport challenges the concept of rigid structural models in which ion specificity at site I and site II arises from a precise and unique arrangement of coordinating ligands. Furthermore, actions by guanidinium+ derivatives suggest that Na+ binds to site III in a hydrated form and that the inward current observed without external Na+ and K+ represents cation transport when normal occlusion at sites I and II is impaired. These results provide insights on external ion selectivity at the three binding sites. PMID:20937860

Motif discovery with data mining in 3D protein structure databases: discovery, validation and prediction of the U-shape zinc binding ("Huf-Zinc") motif.

PubMed

Maurer-Stroh, Sebastian; Gao, He; Han, Hao; Baeten, Lies; Schymkowitz, Joost; Rousseau, Frederic; Zhang, Louxin; Eisenhaber, Frank

2013-02-01

Data mining in protein databases, derivatives from more fundamental protein 3D structure and sequence databases, has considerable unearthed potential for the discovery of sequence motif--structural motif--function relationships as the finding of the U-shape (Huf-Zinc) motif, originally a small student's project, exemplifies. The metal ion zinc is critically involved in universal biological processes, ranging from protein-DNA complexes and transcription regulation to enzymatic catalysis and metabolic pathways. Proteins have evolved a series of motifs to specifically recognize and bind zinc ions. Many of these, so called zinc fingers, are structurally independent globular domains with discontinuous binding motifs made up of residues mostly far apart in sequence. Through a systematic approach starting from the BRIX structure fragment database, we discovered that there exists another predictable subset of zinc-binding motifs that not only have a conserved continuous sequence pattern but also share a characteristic local conformation, despite being included in totally different overall folds. While this does not allow general prediction of all Zn binding motifs, a HMM-based web server, Huf-Zinc, is available for prediction of these novel, as well as conventional, zinc finger motifs in protein sequences. The Huf-Zinc webserver can be freely accessed through this URL (http://mendel.bii.a-star.edu.sg/METHODS/hufzinc/).

Zinc-ion implanted and deposited titanium surfaces reduce adhesion of Streptococccus mutans

NASA Astrophysics Data System (ADS)

Xu, Juan; Ding, Gang; Li, Jinlu; Yang, Shenhui; Fang, Bisong; Sun, Hongchen; Zhou, Yanmin

2010-10-01

While titanium (Ti) is a commonly used dental implant material with advantageous biocompatible and mechanical properties, native Ti surfaces do not have the ability to prevent bacterial colonization. The objective of this study was to evaluate the chemical composition and bacterial adhesive properties of zinc (Zn) ion implanted and deposited Ti surfaces (Zn-PIIID-Ti) as potential dental implant materials. Surfaces of pure Ti (cp-Ti) were modified with increasing concentrations of Zn using plasma immersion ion implantation and deposition (PIIID), and elemental surface compositions were characterized by X-ray photoelectron spectrometry (XPS). To evaluate bacterial responses, Streptococcus mutans were seeded onto the modifiedTi surfaces for 48 h and subsequently observed by scanning electron microscopy. Relative numbers of bacteria on each surface were assessed by collecting the adhered bacteria, reculturing and counting colony forming units after 48 h on bacterial grade plates. Ti, oxygen and carbon elements were detected on all surfaces by XPS. Increased Zn signals were detected on Zn-PIIID-Ti surfaces, correlating with an increase of Zn-deposition time. Substantial numbers of S. mutans adhered to cp-Ti samples, whereas bacterial adhesion on Zn-PIIID-Ti surfaces signficantly decreased as the Zn concentration increased ( p < 0.01). In conclusion, PIIID can successfully introduce Zn onto a Ti surface, forming a modified surface layer bearing Zn ions that consequently deter adhesion of S. mutans, a common bacterium in the oral environment.

Flexibility of Catalytic Zinc Coordination in Thermolysin and HDAC8: A Born-Oppenheimer ab initio QM/MM Molecular Dynamics Study

PubMed Central

Wu, Ruibo; Hu, Po; Wang, Shenglong; Cao, Zexing; Zhang, Yingkai

2009-01-01

Abstracs The different coordination modes and fast ligand exchange of zinc coordination has been suggested to be one key catalytic feature of the zinc ion which makes it an invaluable metal in biological catalysis. However, partly due to the well known difficulties for zinc to be characterized by spectroscopy methods, evidence for dynamic nature of the catalytic zinc coordination has so far mainly been indirect. In this work, Born-Oppenheimer ab initio QM/MM molecular dynamics simulation has been employed, which allows for a first-principle description of the dynamics of the metal active site while properly including effects of the heterogeneous and fluctuating protein environment. Our simulations have provided direct evidence regarding inherent flexibility of the catalytic zinc coordination shell in Thermolysin (TLN) and Histone Deacetylase 8 (HDAC8). We have observed different coordination modes and fast ligand exchange during the picosecond's time-scale. For TLN, the coordination of the carboxylate group of Glu166 to Zinc is found to continuously change between monodentate and bidentate manner dynamically; while for HDAC8, the flexibility mainly comes from the coordination to a non-amino-acid ligand. Such distinct dynamics in the zinc coordination shell between two enzymes suggests that the catalytic role of Zinc in TLN and HDAC8 is likely to be different in spite of the fact that both catalyze the hydrolysis of amide bond. Meanwhile, considering that such Born-Oppenheimer ab initio QM/MM MD simulations are very much desired but are widely considered to be too computationally expensive to be feasible, our current study demonstrates the viability and powerfulness of this state-of-the-art approach in simulating metalloenzymes. PMID:20161624

Combined experimental and theoretical studies on selective sensing of zinc and pyrophosphate ions by rational design of compartmental chemosensor probe: Dual sensing behaviour via secondary recognition approach and cell imaging studies.

PubMed

Mawai, Kiran; Nathani, Sandip; Roy, Partha; Singh, U P; Ghosh, Kaushik

2018-05-08

A compartmental chemosensor probe HL has been designed and synthesized for the selective recognition of zinc ions over other transition metal ions via fluorescence "ON" strategy. The chemosensing behaviour of HL was demonstrated through fluorescence, absorption and NMR spectroscopic techniques. The molecular structure of the zinc complex derived from HL was determined by X-ray crystallography. A probable mechanism of this selective sensing behavior was described on the basis of spectroscopic results and theoretical studies by density functional theory (DFT). The biological applicability of the chemosensor HL was examined via cell imaging on HeLa cells. The HL-zinc complex served as a secondary fluorescent probe responding to the pyrophosphate anion specifically over other anions. The fluorescence enhancement of HL in association with Zn2+ ions was quenched in the presence of pyrophosphate (PPi). Thus, a dual response was established based on "OFF-ON-OFF" strategy for detection of both cation and anion. This phenomenon was utilized in the construction of a "INHIBIT" logic gate.

Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors

PubMed Central

Chorny, Michael; Fishbein, Ilia; Tengood, Jillian E.; Adamo, Richard F.; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

Gene therapeutic strategies have shown promise in treating vascular disease. However, their translation into clinical use requires pharmaceutical carriers enabling effective, site-specific delivery as well as providing sustained transgene expression in blood vessels. While replication-deficient adenovirus (Ad) offers several important advantages as a vector for vascular gene therapy, its clinical applicability is limited by rapid inactivation, suboptimal transduction efficiency in vascular cells, and serious systemic adverse effects. We hypothesized that novel zinc oleate-based magnetic nanoparticles (MNPs) loaded with Ad would enable effective arterial cell transduction by shifting vector processing to an alternative pathway, protect Ad from inactivation by neutralizing factors, and allow site-specific gene transfer to arteries treated with stent angioplasty using a 2-source magnetic guidance strategy. Ad-loaded MNPs effectively transduced cultured endothelial and smooth muscle cells under magnetic conditions compared to controls and retained capacity for gene transfer after exposure to neutralizing antibodies and lithium iodide, a lytic agent causing disruption of free Ad. Localized arterial gene expression significantly stronger than in control animal groups was demonstrated after magnetically guided MNP delivery in a rat stenting model 2 and 9 d post-treatment, confirming feasibility of using Ad-loaded MNPs to achieve site-specific transduction in stented blood vessels. In conclusion, Ad-loaded MNPs formed by controlled precipitation of zinc oleate represent a novel delivery system, well-suited for efficient, magnetically targeted vascular gene transfer.—Chorny, M., Fishbein, I., Tengood, J. E., Adamo, R. F., Alferiev, I. S., Levy, R. J. Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors. PMID:23407712

Growth and characterization of divalent transition metal ions doped zinc hydrogen phosphate single crystals

NASA Astrophysics Data System (ADS)

D'Souza, Delma; Jagannatha, N.; Nagaraja, K. P.; Rohith, P. S.; Pradeepkumar, K. V.

2018-05-01

Zinc hydrogen phosphate (ZnHP) single crystal co-doped with divalent transition metal ions Cobalt (Co2+) and Cadmium (Cd2+) is grown by gel technique in silica hydro gel media. The presence of Co2+ and Cd2+ dopants in the ZnHP crystal was confirmed by Energy Dispersive X-ray Analysis (EDAX).FTIR spectra of the grown crystal depict the stretching and bending vibration of PO4 units, water of crystallization and metal-oxygen bonds. Powder XRD analysis reveals that the grown crystal belongs to monoclinic system with spacegroup P 21. The thermal stability of the grown crystal is rectified from TG-DSC studies.

Active sites for CO 2 hydrogenation to methanol on Cu/ZnO catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kattel, Shyam; Ramírez, Pedro J.; Chen, Jingguang G.

The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al 2O 3) catalysts for carbon dioxide (CO 2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. Here, we report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO andmore » allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. These results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.« less

Active sites for CO 2 hydrogenation to methanol on Cu/ZnO catalysts

DOE PAGES

Kattel, Shyam; Ramírez, Pedro J.; Chen, Jingguang G.; ...

2017-03-23

The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al 2O 3) catalysts for carbon dioxide (CO 2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. Here, we report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO andmore » allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. These results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.« less

Reexamining the functions of zinc sulfate as a selective depressant in differential sulfide flotation--the role of coagulation.

PubMed

Cao, Mingli; Liu, Qi

2006-09-15

Zinc sulfate is a well-known selective depressant for zinc sulfide minerals such as sphalerite during the flotation of complex Cu-Pb-Zn sulfide ores. It deactivates sphalerite flotation by substituting the activating metal ions, and depresses sphalerite flotation by forming hydrophilic coatings of zinc hydroxyl species on sphalerite surfaces. However, we recently observed that zinc sulfate could also induce coagulation of fine sphalerite particles and such coagulation significantly reduced the mechanical entrainment of the fine sphalerite. Therefore, it seems that the effectiveness of zinc sulfate as a selective sphalerite depressant is not only due to its ability to make mineral surface hydrophilic, which reduces genuine flotation, but also due to its ability to coagulate the mineral, which reduces mechanical entrainment. Zinc sulfate is a "dual function" selective flotation depressant.

Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc Superoxide Dismutase*

PubMed Central

Sea, Kevin; Sohn, Se Hui; Durazo, Armando; Sheng, Yuewei; Shaw, Bryan F.; Cao, Xiaohang; Taylor, Alexander B.; Whitson, Lisa J.; Holloway, Stephen P.; Hart, P. John; Cabelli, Diane E.; Gralla, Edith Butler; Valentine, Joan Selverstone

2015-01-01

The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. We determined x-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. The addition of copper to this four-zinc protein gave properly reconstituted 2Cu,2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild type hSOD1. In contrast, the addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at ∼10% of the wild type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. Saccharomyces cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30–50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity. PMID:25433341

Recent advances in zinc-air batteries.

PubMed

Li, Yanguang; Dai, Hongjie

2014-08-07

Zinc-air is a century-old battery technology but has attracted revived interest recently. With larger storage capacity at a fraction of the cost compared to lithium-ion, zinc-air batteries clearly represent one of the most viable future options to powering electric vehicles. However, some technical problems associated with them have yet to be resolved. In this review, we present the fundamentals, challenges and latest exciting advances related to zinc-air research. Detailed discussion will be organized around the individual components of the system - from zinc electrodes, electrolytes, and separators to air electrodes and oxygen electrocatalysts in sequential order for both primary and electrically/mechanically rechargeable types. The detrimental effect of CO2 on battery performance is also emphasized, and possible solutions summarized. Finally, other metal-air batteries are briefly overviewed and compared in favor of zinc-air.

Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers.

PubMed Central

De Rocquigny, H; Gabus, C; Vincent, A; Fournié-Zaluski, M C; Roques, B; Darlix, J L

1992-01-01

The nucleocapsid (NC) of human immunodeficiency virus type 1 consists of a large number of NC protein molecules, probably wrapping the dimeric RNA genome within the virion inner core. NC protein is a gag-encoded product that contains two zinc fingers flanked by basic residues. In human immunodeficiency virus type 1 virions, NCp15 is ultimately processed into NCp7 and p6 proteins. During virion assembly the retroviral NC protein is necessary for core formation and genomic RNA encapsidation, which are essential for virus infectivity. In vitro NCp15 activates viral RNA dimerization, a process most probably linked in vivo to genomic RNA packaging, and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. To characterize the domains of human immunodeficiency virus type 1 NC protein necessary for its various functions, the 72-amino acid NCp7 and several derived peptides were synthesized in a pure form. We show here that synthetic NCp7 with or without the two zinc fingers has the RNA annealing activities of NCp15. Further deletions of the N-terminal 12 and C-terminal 8 amino acids, leading to a 27-residue peptide lacking the finger domains, have little or no effect on NC protein activity in vitro. However deletion of short sequences containing basic residues flanking the first finger leads to a complete loss of NC protein activity. It is proposed that the basic residues and the zinc fingers cooperate to select and package the genomic RNA in vivo. Inhibition of the viral RNA binding and annealing activities associated with the basic residues flanking the first zinc finger of NC protein could therefore be used as a model for the design of antiviral agents. Images PMID:1631144

Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers.

PubMed

De Rocquigny, H; Gabus, C; Vincent, A; Fournié-Zaluski, M C; Roques, B; Darlix, J L

1992-07-15

The nucleocapsid (NC) of human immunodeficiency virus type 1 consists of a large number of NC protein molecules, probably wrapping the dimeric RNA genome within the virion inner core. NC protein is a gag-encoded product that contains two zinc fingers flanked by basic residues. In human immunodeficiency virus type 1 virions, NCp15 is ultimately processed into NCp7 and p6 proteins. During virion assembly the retroviral NC protein is necessary for core formation and genomic RNA encapsidation, which are essential for virus infectivity. In vitro NCp15 activates viral RNA dimerization, a process most probably linked in vivo to genomic RNA packaging, and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. To characterize the domains of human immunodeficiency virus type 1 NC protein necessary for its various functions, the 72-amino acid NCp7 and several derived peptides were synthesized in a pure form. We show here that synthetic NCp7 with or without the two zinc fingers has the RNA annealing activities of NCp15. Further deletions of the N-terminal 12 and C-terminal 8 amino acids, leading to a 27-residue peptide lacking the finger domains, have little or no effect on NC protein activity in vitro. However deletion of short sequences containing basic residues flanking the first finger leads to a complete loss of NC protein activity. It is proposed that the basic residues and the zinc fingers cooperate to select and package the genomic RNA in vivo. Inhibition of the viral RNA binding and annealing activities associated with the basic residues flanking the first zinc finger of NC protein could therefore be used as a model for the design of antiviral agents.

Effect of phytate and zinc ions on fluoride toothpaste efficacy using an in situ caries model.

PubMed

Parkinson, Charles R; Burnett, Gary R; Creeth, Jonathan E; Lynch, Richard J M; Budhawant, Chandrashekhar; Lippert, Frank; Hara, Anderson T; Zero, Domenick T

2018-06-01

To compare and explore the dose-response of phytate-containing 1150 ppm fluoride toothpastes on model caries lesions and to determine the impact of zinc ions. This was a single-centre, randomised, blinded (examiner/laboratory analyst), six-treatment, four-period crossover, in situ study in adults with a removable bilateral maxillary partial denture. Study treatments were toothpastes containing: 0.425% phytate/F; 0.85% phytate/F; 0.85% phytate/Zn/F; F-only; Zn/F and a 0% F placebo. Where present, F was 1150 ppm as NaF; Zn was 0.3% as ZnCl 2 . Human enamel specimens containing early-stage, surface-softened (A-lesions) or more advanced, subsurface (B-lesions) caries lesions were placed into the buccal flanges of participants' modified partial denture (one of each lesion type per side). A-lesions were removed after 14 days of twice-daily treatment use; B-lesions were removed after a further 14 days. A-lesions were analysed for surface microhardness recovery. Both lesion types were analysed by transverse microradiography and for enamel fluoride uptake, with B-lesions additionally analysed by quantitative light-induced fluorescence. Comparison was carried out using an analysis of covariance model. Statistically significant differences between 1150 ppm F and the placebo toothpastes (p < 0.05) were shown for all measures, validating the model. No differences between fluoride toothpastes were observed for any measure with little evidence of a dose-response for phytate. Study treatments were generally well-tolerated. Results suggest phytate has little impact on fluoride's ability to promote early-stage lesion remineralisation or prevent more advanced lesion demineralisation in this in situ caries model. Similarly, results suggest zinc ions do not impair fluoride efficacy. Toothpastes may contain therapeutic or cosmetic agents that could interfere with fluoride's caries prevention efficacy. The present in situ caries study has demonstrated that phytate, added to

Barium and manganese-doped zinc silicate rods prepared by mesoporous template route and their luminescence property

NASA Astrophysics Data System (ADS)

Dang, Lingyan; Tian, Chen; Zhao, Shifeng; Lu, Qingshan

2018-06-01

Barium and manganese-doped zinc silicates was prepared under hydrothermal treatment by mesoporous template route employing mesoporous silica as an active template. The sample displays a rod-like morphology with a mean diameter of ∼40 nm and a mean length of ∼450 nm, which inherits the characteristics of mesoporous silica. The individual rods show single crystalline and assemble into bundle-like hierarchical structure along the channels of the mesoporous silica. When barium ions together with manganese ions are co-doped in zinc silicate, the green emission corresponding to manganese ions display a significant enhancement, especially for the sample with the barium doping concentration of 0.08, which indicates that an energy transfer from barium to manganese ions takes place. With further increasing barium concentration from 0.08 to 0.10, the recombination between the defects related to barium and the excitation states of the manganese dominates accompanying non-radiative transitions which can reduce the emission efficiency.

Facile synthesis and photocatalytic activity of ZnO/zinc titanate core-shell nanorod arrays

NASA Astrophysics Data System (ADS)

He, Ding-Chao; Fu, Qiu-Ming; Ma, Zhi-Bin; Zhao, Hong-Yang; Tu, Ya-Fang; Tian, Yu; Zhou, Di; Zheng, Guang; Lu, Hong-Bing

2018-02-01

ZnO/zinc titanate core-shell nanorod arrays (CSNRs) were successfully prepared via a simple synthesis process by combining hydrothermal synthesis and liquid phase deposition (LPD). The surface morphologies, crystalline characteristics, optical properties and surface electronic states of the ZnO/zinc titanate CSNRs were characterized by scanning electron microscope, transmission electron microscope, x-ray diffractometer, x-ray photoelectron spectroscopy, PL and ultraviolet (UV)-visible absorption spectra. By controlling the reaction time of LPD, the shell thickness could vary with the reaction time. Furthermore, the impacts of the reaction time and post-annealing temperature on the crystalline structure and chemical composition of the CSNRs were also investigated. The studies of photocatalytic activity under UV light irradiation revealed that the ZnO/zinc titanate CSNRs annealed at 700 °C with 30 min deposition exhibited the best photocatalytic activity and good stability for degradation of methylene blue. It had been found that the effective separation of photogenerated electron-hole pairs in the CSNRs led to the enhanced photocatalytic activity. Moreover, the ZnO/zinc titanate CSNRs grown on quartz glass substrate could be easily recycled for reuse with almost unchanged photocatalytic activity.

Ionizable side chains at catalytic active sites of enzymes.

PubMed

Jimenez-Morales, David; Liang, Jie; Eisenberg, Bob

2012-05-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å(3). The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.

X-ray-induced fluorescent centers formation in zinc- phosphate glasses doped with Ag and Cu ions

NASA Astrophysics Data System (ADS)

Klyukin, D. A.; Pshenova, A. S.; Sidorov, A. I.; Stolyarchuk, M. V.

2016-08-01

Fluorescent properties of silver and copper doped zinc-phosphate glasses were studied. By X-ray irradiation of silver and copper co-doped glasses we could create and identify new emission centers which do not exist in single-doped samples. Doping of the glass with both silver and copper ions leads to the increase of quantum yield by 2.7 times. The study was complemented by quantum chemical calculations using the time-dependent density functional theory. It was shown that fluorescence may be attributed to the formation of mixed Ag-Cu molecular clusters.

ttm-1 Encodes CDF Transporters That Excrete Zinc from Intestinal Cells of C. elegans and Act in a Parallel Negative Feedback Circuit That Promotes Homeostasis

PubMed Central

Roh, Hyun Cheol; Collier, Sara; Deshmukh, Krupa; Guthrie, James; Robertson, J. David; Kornfeld, Kerry

2013-01-01

Zinc is an essential metal involved in a wide range of biological processes, and aberrant zinc metabolism is implicated in human diseases. The gastrointestinal tract of animals is a critical site of zinc metabolism that is responsible for dietary zinc uptake and distribution to the body. However, the role of the gastrointestinal tract in zinc excretion remains unclear. Zinc transporters are key regulators of zinc metabolism that mediate the movement of zinc ions across membranes. Here, we identified a comprehensive list of 14 predicted Cation Diffusion Facilitator (CDF) family zinc transporters in Caenorhabditis elegans and demonstrated that zinc is excreted from intestinal cells by one of these CDF proteins, TTM-1B. The ttm-1 locus encodes two transcripts, ttm-1a and ttm-1b, that use different transcription start sites. ttm-1b expression was induced by high levels of zinc specifically in intestinal cells, whereas ttm-1a was not induced by zinc. TTM-1B was localized to the apical plasma membrane of intestinal cells, and analyses of loss-of-function mutant animals indicated that TTM-1B promotes zinc excretion into the intestinal lumen. Zinc excretion mediated by TTM-1B contributes to zinc detoxification. These observations indicate that ttm-1 is a component of a negative feedback circuit, since high levels of cytoplasmic zinc increase ttm-1b transcript levels and TTM-1B protein functions to reduce the level of cytoplasmic zinc. We showed that TTM-1 isoforms function in tandem with CDF-2, which is also induced by high levels of cytoplasmic zinc and reduces cytoplasmic zinc levels by sequestering zinc in lysosome-related organelles. These findings define a parallel negative feedback circuit that promotes zinc homeostasis and advance the understanding of the physiological roles of the gastrointestinal tract in zinc metabolism in animals. PMID:23717214

Automatically activated, 300 ampere-hour silver-zinc cell

NASA Technical Reports Server (NTRS)

Hennigan, T. J.

1972-01-01

A prototype silver zinc cell is reported for which the electrolyte is being stored in a separate tank; the cell is being activated when additional power is required by collapsing the neoprene bellows container and thus forcing the electrolyte into cell through a plastic connection. A solar array is proposed as main power source for the flow actuator.

Role of zinc and α2macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma

PubMed Central

Mocchegiani, E; Ciavattini, A; Santarelli, L; Tibaldi, A; Muzzioli, M; Bonazzi, P; Giacconi, R; Fabris, N; Garzetti, G G

1999-01-01

Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. α2-Macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because α2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35–60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2–IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented α2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and α2-macroglobulin (r = 0.75, P< 0.01, r = 0.78, P< 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in α2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency. © 1999 Cancer Research Campaign PMID:9888464

ZINC: A Free Tool to Discover Chemistry for Biology

PubMed Central

2012-01-01

ZINC is a free public resource for ligand discovery. The database contains over twenty million commercially available molecules in biologically relevant representations that may be downloaded in popular ready-to-dock formats and subsets. The Web site also enables searches by structure, biological activity, physical property, vendor, catalog number, name, and CAS number. Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org. PMID:22587354

Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity☆

PubMed Central

Milacic, Vesna; Chen, Di; Giovagnini, Lorena; Diez, Alejandro; Fregona, Dolores; Dou, Q. Ping

2013-01-01

Zinc and copper are trace elements essential for proper folding, stabilization and catalytic activity of many metalloenzymes in living organisms. However, disturbed zinc and copper homeostasis is reported in many types of cancer. We have previously demonstrated that copper complexes induced proteasome inhibition and apoptosis in cultured human cancer cells. In the current study we hypothesized that zinc complexes could also inhibit the proteasomal chymotrypsin-like activity responsible for subsequent apoptosis induction. We first showed that zinc(II) chloride was able to inhibit the chymotrypsin-like activity of a purified 20S proteasome with an IC50 value of 13.8 μM, which was less potent than copper(II) chloride (IC50 5.3 μM). We then compared the potencies of a pyrrolidine dithiocarbamate (PyDT)-zinc(II) complex and a PyDT-copper(II) complex to inhibit cellular proteasomal activity, suppress proliferation and induce apoptosis in various human breast and prostate cancer cell lines. Consistently, zinc complex was less potent than copper complex in inhibiting the proteasome and inducing apoptosis. Additionally, zinc and copper complexes appear to use somewhat different mechanisms to kill tumor cells. Zinc complexes were able to activate calpain-, but not caspase-3-dependent pathway, while copper complexes were able to induce activation of both proteases. Furthermore, the potencies of these PyDT-metal complexes depend on the nature of metals and also on the ratio of PyDT to the metal ion within the complex, which probably affects their stability and availability for interacting with and inhibiting the proteasome in tumor cells. PMID:18501397

Serum thymulin in human zinc deficiency.

PubMed Central

Prasad, A S; Meftah, S; Abdallah, J; Kaplan, J; Brewer, G J; Bach, J F; Dardenne, M

1988-01-01

The activity of thymulin (a thymic hormone) is dependent on the presence of zinc in the molecule. We assayed serum thymulin activity in three models of mildly zinc-deficient (ZD) human subjects before and after zinc supplementation: (a) two human volunteers in whom a specific and mild zinc deficiency was induced by dietary means; (b) six mildly ZD adult sickle cell anemia (SCA) subjects; and (c) six mildly ZD adult non-SCA subjects. Their plasma zinc levels were normal and they showed no overt clinical manifestations of zinc deficiency. The diagnosis of mild zinc deficiency was based on the assay of zinc in lymphocytes, granulocytes, and platelets. Serum thymulin activity was decreased as a result of mild zinc deficiency and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter was a sensitive indicator of zinc deficiency in humans. An increase in T101-, sIg-cells, decrease in T4+/T8+ ratio, and decreased IL 2 activity were observed in the experimental human model during the zinc depletion phase, all of which were corrected after repletion with zinc. Similar changes in lymphocyte subpopulation, correctable with zinc supplementation, were also observed in mildly ZD SCA subjects. Inasmuch as thymulin is known to induce intra- and extrathymic T cell differentiation, our studies provide a possible mechanism for the role of zinc on T cell functions. Images PMID:3262625

Evaluation of layered zinc hydroxide nitrate and zinc/nickel double hydroxide salts in the removal of chromate ions from solutions

NASA Astrophysics Data System (ADS)

de Oliveira, Henrique Bortolaz; Wypych, Fernando

2016-11-01

Layered zinc hydroxide nitrate (ZnHN) and Zn/Ni layered double hydroxide salts were synthesized and used to remove chromate ions from solutions at pH 8.0. The materials were characterized by many instrumental techniques before and after chromate ion removal. ZnHN decomposed after contact with the chromate solution, whereas the layered structure of Zn/Ni hydroxide nitrate (Zn/NiHN) and Zn/Ni hydroxide acetate (Zn/NiHA) remained their layers intact after the topotactic anionic exchange reaction, only changing the basal distances. ZnHN, Zn/NiHN, and Zn/NiHA removed 210.1, 144.8, and 170.1 mg of CrO42-/g of material, respectively. Although the removal values obtained for Zn/NiHN and Zn/NiHA were smaller than the values predicted for the ideal formulas of the solids (194.3 and 192.4 mg of CrO42-/g of material, respectively), the measured capacities were higher than the values achieved with many materials reported in the literature. Kinetic experiments showed the removal reaction was fast. To facilitate the solid/liquid separation process after chromium removal, Zn/Ni layered double hydroxide salts with magnetic supports were also synthesized, and their ability to remove chromate was evaluated.

Calcium ions rescue human lung epithelial cells from the toxicity of zinc oxide nanoparticles.

PubMed

Hanagata, Nobutaka; Morita, Hiromi

2015-01-01

Contradictory results have been reported for in vitro evaluations of whether zinc oxide nanoparticles (ZnO NPs) are cytotoxic. Though there have been reports of ZnO NPs cytotoxicity due to Zn ions released from the nanoparticles, there have also been reports concluding that Zn ions are not cytotoxic. This inconsistency is mostly attributed to the types of cells used. In this research, we investigated the difference in the level of ZnO NPs cytotoxicity due to culturing conditions. The sensitivity of human lung epithelial cells to ZnO NPs cytotoxicity differed depending on the dispersing medium, physiological state of the cells resulting from their growth stage, and composition of the medium. Further, with regard to the toxicity of ZnO NPs, NPs internalized into cells had a greater cytotoxic effect than Zn ions released from ZnO NPs. Instead of inducing cell death, ZnO NPs internalized into cells slowed the rate of cell proliferation. Furthermore, the cytotoxicity of ZnO NPs depended greatly on the concentration of calcium ions (Ca2+) in the medium. When the concentration of Ca2+ was low, the cytotoxicity of ZnO NPs increased markedly. However, the toxicity of ZnO NPs was mitigated by the addition of CaCl2 to the medium. Global gene expression analysis revealed that Ca2+ -induced upregulation of cell cycle functions could be attributable to the mitigation of ZnO NP toxicity by Ca2+.

EPR study of copper(II) ions in zinc 1-malate trihydrate

NASA Astrophysics Data System (ADS)

Bonomo, Raffaele P.; Di Bilio, Angel J.; Riggi, Francesco

1988-10-01

The EPR spectrum of Cu 2+ ions in zinc 1-malate trihydrate has been measured at 150 K for a large number of orientations of the applied magnetic field. Analysis yields the following spin Hamiltonian parameters: g x=2.0894±0.0009, A x=-12.0±1.5, g y=2.0879±0.0005, A y=-8.7±1.0, R=-0.7±1.5, g z=2.4249±0.0005, A z=-120.1±0.9, P=9.9±0.5, where the units of A and P are 10 4 cm -1. The Zeeman and hyperfine coupling tensors are coincident within 2°. The spectrum shows forbidden transitions with abnormal intensity due to a large quadrupolar interaction. The direction of g z points towards the hydroxyl oxygen while the g x and g y directions lie approximately along the metal-carboxylate oxygen bond.

A facile synthesis of zinc oxide/multiwalled carbon nanotube nanocomposite lithium ion battery anodes by sol-gel method

NASA Astrophysics Data System (ADS)

Köse, Hilal; Karaal, Şeyma; Aydın, Ali Osman; Akbulut, Hatem

2015-11-01

Free standing zinc oxide (ZnO) and multiwalled carbon nanotube (MWCNT) nanocomposite materials are prepared by a sol gel technique giving a new high capacity anode material for lithium ion batteries. Free-standing ZnO/MWCNT nanocomposite anodes with two different chelating agent additives, triethanolamine (TEA) and glycerin (GLY), yield different electrochemical performances. Field emission gun scanning electron microscopy (FEG-SEM), energy dispersive X-ray spectrometer (EDS), high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) analyses reveal the produced anode electrodes exhibit a unique structure of ZnO coating on the MWCNT surfaces. Li-ion cell assembly using a ZnO/MWCNT/GLY free-standing anode and Li metal cathode possesses the best discharge capacity, remaining as high as 460 mAh g-1 after 100 cycles. This core-shell structured anode can offer increased energy storage and performance over conventional anodes in Li-ion batteries.

The Cysteine-rich Domain of the DHHC3 Palmitoyltransferase Is Palmitoylated and Contains Tightly Bound Zinc*

PubMed Central

Gottlieb, Colin D.; Zhang, Sheng; Linder, Maurine E.

2015-01-01

DHHC palmitoyltransferases catalyze the addition of the fatty acid palmitate to proteins on the cytoplasmic leaflet of cell membranes. There are 23 members of the highly diverse mammalian DHHC protein family, all of which contain a conserved catalytic domain called the cysteine-rich domain (CRD). DHHC proteins transfer palmitate via a two-step catalytic mechanism in which the enzyme first modifies itself with palmitate in a process termed autoacylation. The enzyme then transfers palmitate from itself onto substrate proteins. The number and location of palmitoylated cysteines in the autoacylated intermediate is unknown. In this study, we present evidence using mass spectrometry that DHHC3 is palmitoylated at the cysteine in the DHHC motif. Mutation of highly conserved CRD cysteines outside the DHHC motif resulted in activity deficits and a structural perturbation revealed by limited proteolysis. Treatment of DHHC3 with chelating agents in vitro replicated both the specific structural perturbations and activity deficits observed in conserved cysteine mutants, suggesting metal ion-binding in the CRD. Using the fluorescent indicator mag-fura-2, the metal released from DHHC3 was identified as zinc. The stoichiometry of zinc binding was measured as 2 mol of zinc/mol of DHHC3 protein. Taken together, our data demonstrate that coordination of zinc ions by cysteine residues within the CRD is required for the structural integrity of DHHC proteins. PMID:26487721

Zinc and magnesium ions synergistically inhibit superoxide generation by cultured human neutrophils--a promising candidate formulation for amnioinfusion fluid.

PubMed

Uchida, Toshiyuki; Itoh, Hiroaki; Nakamura, Yuki; Kobayashi, Yukiko; Hirai, Kyuya; Suzuki, Kazunao; Sugihara, Kazuhiro; Kanayama, Naohiro; Hiramatsu, Mitsuo

2010-06-01

Oligohydramnios is often caused by the premature rupturing of membranes and subsequent intrauterine infections, such as chorioamnionitis, in which event oxidative stress is hypothesized to be closely associated with the damage to the fetal organs. The clinical efficiency of amnioinfusion using warmed saline in cases of premature rupture of membranes is still controversial, especially concerning the prognosis for the fetus. In the present study, we found that human amniotic fluid per se suppresses the release of superoxide from cultured human neutrophils, suggesting an acute or chronic shortage of amniotic fluid in cases of premature rupture of membranes can affect the shielding of intrauterine organs from oxidative stress. The aim of this study was to propose a formula of zinc and magnesium ions in saline for amnioinfusion, by assessing antioxidative activities. A combination of 5 microM zinc and 5mM magnesium in saline synergistically inhibited superoxide production by cultured human neutrophils, equivalent to human amniotic fluid. The intraperitoneal administration of this formula significantly improved the survival rate in a rat model of peritonitis compared to the saline control (46.7% vs. 10%). The combination of these metals with saline may thus be a promising formula for an amnioinfusion fluid with the capacity to protect fetal organs from oxidative stress. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Zinc is released by cultured astrocytes as a gliotransmitter under hypoosmotic stress-loaded conditions and regulates microglial activity.

PubMed

Segawa, Shohei; Nishiura, Takeshi; Furuta, Takahiro; Ohsato, Yuki; Tani, Misaki; Nishida, Kentaro; Nagasawa, Kazuki

2014-01-17

Astrocytes contribute to the maintenance of brain homeostasis via the release of gliotransmitters such as ATP and glutamate. Here we examined whether zinc was released from astrocytes under stress-loaded conditions, and was involved in the regulation of microglial activity as a gliotransmitter. Hypoosmotic stress was loaded to astrocytes using balanced salt solution prepared to 214-314 mOsmol/L, and then intra- and extra-cellular zinc levels were assessed using Newport Green DCF diacetate (NG) and ICP-MS, respectively. Microglial activation by the astrocytic supernatant was assessed by their morphological changes and poly(ADP-ribose) (PAR) polymer accumulation. Exposure of astrocytes to hypoosmotic buffer, increased the extracellular ATP level in osmolarity-dependent manners, indicating a load of hypoosmotic stress. In hypoosmotic stress-loaded astrocytes, there were apparent increases in the intra- and extra-cellular zinc levels. Incubation of microglia in the astrocytic conditioned medium transformed them into the activated "amoeboid" form and induced PAR formation. Administration of an extracellular zinc chelator, CaEDTA, to the astrocytic conditioned medium almost completely prevented the microglial activation. Treatment of astrocytes with an intracellular zinc chelator, TPEN, suppressed the hypoosmotic stress-increased intracellular, but not the extracellular, zinc level, and the increase in the intracellular zinc level was blocked partially by a nitric oxide synthase inhibitor, but not by CaEDTA, indicating that the mechanisms underlying the increases in the intra- and extra-cellular zinc levels might be different. These findings suggest that under hypoosmotic stress-loaded conditions, zinc is released from astrocytes and then plays a primary role in microglial activation as a gliotransmitter. Copyright © 2013 Elsevier Inc. All rights reserved.

Anticancer activity of fungal L-asparaginase conjugated with zinc oxide nanoparticles.

PubMed

Baskar, G; Chandhuru, J; Sheraz Fahad, K; Praveen, A S; Chamundeeswari, M; Muthukumar, T

2015-01-01

Demand for developing novel delivery system for cancer treatment has increased due to the side effects present in intravenous injection of L-asparaginase. Nanoparticles are used for delivering the drugs to its destination in cancer cure. Nanobiocomposite of zinc oxide nanoparticles conjugated with L-asparaginase was produced by Aspergillus terreus and was confirmed using maximum UV-Vis absorption at 340 nm in the present work. The presence of functional groups like OH, C-H, -C=N and C=O on the surface of nanobiocomposite was found from Fourier transform infrared spectrum analysis. Size of the produced nanocomposite was found in the range of 28-63 nm using scanning electron microscope. The crystalline nature of the synthesized nanobiocomposites was confirmed by X-ray diffraction analysis. The presence of zinc oxide on synthesized nanobiocomposite was confirmed by energy dispersive spectrum analysis. The anti-cancerous nature of the synthesized zinc oxide conjugated L-asparaginase nanobiocomposite on MCF-7 cell line was studied using MTT assay. The viability of the MCF-7 cells was decreased to 35.02 % when it was treated with L-asparaginase conjugated zinc oxide nanobiocomposite. Hence it is proved that the synthesized nanobiocomposites of zinc oxide conjugated L-asparaginase has good anti-cancerous activity.

Long Life, High Energy Silver-Zinc Batteries

NASA Technical Reports Server (NTRS)

Kainthla, Ramesh; Coffey, Brendan

2003-01-01

This viewgraph presentation includes: 1) an introduction to RBC Technologies; 2) Rechargeable Zinc Alkaline (RZA(tm)) Systems which include MnO2/Zn, Ni/Zn, Ag/Zn, and Zn/Air; and 3) RZA Silver/Zinc Battery Developments. Conclusions include the following: 1)Issues with long term wet life and cycle life of the silver/zinc battery system are being overcome through the use of new anode formulations and separator designs; 2) Performance may exceed 200 cycles to 80% of initial capacity and ultimate wet-life of > 36 months; and 3) Rechargeable silver/zinc batteries available in prismatic and cylindrical formats may provide a high energy, high power alternative to lithium-ion in military/aerospace applications.

Inhibition of presynaptic activity by zinc released from mossy fiber terminals during tetanic stimulation.

PubMed

Minami, Akira; Sakurada, Naomi; Fuke, Sayuri; Kikuchi, Kazuya; Nagano, Tetsuo; Oku, Naoto; Takeda, Atsushi

2006-01-01

Zinc exists in high densities in the giant boutons of hippocampal mossy fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from mossy fibers during high-frequency (tetanic) stimulation was examined using hippocampal slices. The increase in zinc-specific fluorescent signals was observed in both extracellular and intracellular compartments in the mossy fiber terminals during the delivery of tetanic stimuli (100 Hz, 1 sec) to the dentate granule cell layer, suggesting that zinc released from mossy fibers is immediately retaken up by mossy fibers. When mossy fiber terminals were preferentially double-stained with zinc and calcium indicators and tetanic stimuli (100 Hz, 1 sec) were delivered to the dentate granule cell layer, the increase in calcium orange signal during the stimulation was enhanced in mossy fiber terminals by addition of CaEDTA, a membrane-impermeable zinc chelator, and was suppressed by addition of zinc. The decrease in FM4-64 signal (vesicular exocytosis) during tetanic stimulation (10 Hz, 180 sec), which induced mossy fiber long-term potentiation, was also enhanced in mossy fiber terminals by addition of CaEDTA and was suppressed by addition of zinc. The present study demonstrates that zinc released from mossy fibers may be a negative-feedback factor against presynaptic activity during tetanic stimulation.

Inhibition of vaccinia virus maturation by zinc chloride.

PubMed Central

Katz, E; Margalith, E

1981-01-01

Zinc chloride (0.1 mM) inhibited by 96.4% the growth of vaccinia virus in HeLa cells. Approximately 50% inhibition in formation of particles that sedimented in sucrose gradients similarly to vaccinia virions occurred in the presence of zinc ions. Whereas the synthesis of the viral deoxyribonucleic acid was not affected by zinc chloride, a decrease in the overall synthesis of viral polypeptides and inhibition of the cleavage of precursors to the core polypeptides were observed. Images PMID:7347557

Effect of short-term zinc supplementation on zinc and selenium tissue distribution and serum antioxidant enzymes.

PubMed

Skalny, Andrey A; Tinkov, Alexey A; Medvedeva, Yulia S; Alchinova, Irina B; Karganov, Mikhail Y; Skalny, Anatoly V; Nikonorov, Alexandr A

2015-01-01

A significant association between Zn and Se homeostasis exists. At the same time, data on the influence of zinc supplementation on selenium distribution in organs and tissues seem to be absent. Therefore, the primary objective of the current study is to investigate the influence of zinc asparaginate supplementation on zinc and selenium distribution and serum superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in Wistar rats. 36 rats were used in the experiment. The duration of the experiment was 7 and 14 days in the first and second series, respectively. The rats in Group I were used as the control ones. Animals in Groups II and III daily obtained zinc asparaginate (ZnA) in the doses of 5 and 15 mg/kg weight, respectively. Zinc and selenium content in liver, kidneys, heart, muscle, serum and hair was assessed using inductively coupled plasma mass spectrometry. Serum SOD and GPx activity was analysed spectrophotometrically using Randox kits. Intragastric administration of zinc asparaginate significantly increased liver, kidney, and serum zinc content without affecting skeletal and cardiac muscle levels. Zinc supplementation also stimulated selenium retention in the rats' organs. Moreover, a significant positive correlation between zinc and selenium content was observed. Finally, zinc asparaginate treatment has been shown to modulate serum GPx but not SOD activity. The obtained data indicate that zinc-induced increase in GPx activity may be mediated through modulation of selenium status. However, future studies are required to estimate the exact mechanisms of zinc and selenium interplay.

Study of zinc-induced changes in lymphocyte membranes using atomic force microscopy, luminescence, and light scattering methods

NASA Astrophysics Data System (ADS)

Filimonenko, D. S.; Khairullina, A. Ya.; Yasinskii, V. M.; Kozlova, N. M.; Zubritskaja, G. P.; Slobozhanina, E. I.

2011-07-01

Changes in the surface structure of lymphocyte membranes exposed to various concentrations of zinc ions are studied. It is found by atomic force microscopy that increasing the concentration of zinc ions leads to a reduction in the correlation length of the autocorrelation function of the roughness profile of a lymphocyte compared to control samples; this may indicate the existence of fine structure in the membrane surface. Fluorescence markers are used to observe a reduction in the microviscosity of the lipids in the outer monolayer of the lipid bilayer after lymphocytes are exposed to Zn ions, as well as the exposure of phosphatidylserine on the surface membrane, and the oxidation of HS-groups of membrane proteins. Calculations of the absorption coefficients of lymphocytes modified with zinc reveal the existence of absorption bands owing to the formation of metal-protein complexes and zinc oxide nanoparticles. These results indicate significant changes in the structural and functional state of lymphocyte membranes exposed to zinc ions.

Possible role of zinc in diminishing lead-related occupational stress-a zinc nutrition concern.

PubMed

Wani, Ab Latif; Ahmad, Ajaz; Shadab, G G H A; Usmani, Jawed Ahmad

2017-03-01

Lead and zinc are mostly present at the same occupational source and usually found as co-contaminants. Lead is known to associate with detrimental effects to humans. Zinc however is an essential nutrient and its deficiency causes debilitating effects on growth and development. Besides, it acts as core ion of important enzymes and proteins. The purpose of this study was to examine if zinc concentrations are associated with blood lead levels and if zinc may prevent lead-induced DNA damage. Blood samples were collected from 92 workers as participants occupationally exposed to lead or lead and zinc and 38 comparison participants having no history of such exposure. Lead and zinc levels were determined from blood by atomic absorption spectrophotometry and genetic damage was assessed by comet assay. Correlation was calculated by Spearman's rho. Lead concentrations were observed to increase among workers with increase in years of exposure. There was a significant difference (p < 0.001) in blood lead levels between workers and controls. In addition, significant difference (p < 0.001) in the genetic damage was observed among workers and controls. A clear effect of increased occupational exposure was visible among workers. Multiple regression analysis further reveals the positive effect of lead, while as the inverse effect of zinc on DNA damage. The results suggest that zinc may influence body lead absorption and may have a role in preventing the genetic damage caused by lead.

Insights into the role of the unusual disulfide bond in copper-zinc superoxide dismutase.

PubMed

Sea, Kevin; Sohn, Se Hui; Durazo, Armando; Sheng, Yuewei; Shaw, Bryan F; Cao, Xiaohang; Taylor, Alexander B; Whitson, Lisa J; Holloway, Stephen P; Hart, P John; Cabelli, Diane E; Gralla, Edith Butler; Valentine, Joan Selverstone

2015-01-23

The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. We determined x-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. The addition of copper to this four-zinc protein gave properly reconstituted 2Cu,2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild type hSOD1. In contrast, the addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at ∼10% of the wild type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. Saccharomyces cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30-50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Ferrate(VI) oxidation of zinc-cyanide complex.

PubMed

Yngard, Ria; Damrongsiri, Seelawut; Osathaphan, Khemarath; Sharma, Virender K

2007-10-01