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NCI Funded Research Portfolio - Z01 BC 005725 Detail

The ABC gene family code for transporter proteins pumping a variety of compounds across the membranes of cells and tissues. Overexpression of ABC transporters is an important cause of multidrug resistance to chemotherapy agents and these genes are mutated in diverse human diseases.

Cancer.gov

2
An ATP-driven efflux pump is a novel pathogenicity factor in rice blast disease.
1999-02-01

Cells tolerate exposure to cytotoxic compounds through the action of ATP-driven efflux pumps belonging to the ATP-binding cassette (ABC) superfamily of membrane transporters. Phytopathogenic fungi encounter toxic environments during plant invasion as a result of the plant defense response. Here we demonstrate the requirement for an ABC ...

PubMed

3
The ABC protein turned chloride channel whose failure causes cystic fibrosis.
2006-03-23

CFTR chloride channels are encoded by the gene mutated in patients with cystic fibrosis. These channels belong to the superfamily of ABC transporter ATPases. ATP-driven conformational changes, which in other ABC proteins fuel uphill substrate transport across cellular membranes, in CFTR open ...

PubMed

4
The ABC protein turned chloride channel whose failure causes cystic fibrosis
2006-03-23

CFTR chloride channels are encoded by the gene mutated in patients with cystic fibrosis. These channels belong to the superfamily of ABC transporter ATPases. ATP-driven conformational changes, which in other ABC proteins fuel uphill substrate transport across cellular membranes, in CFTR open ...

PubMed Central

5
The ABC protein turned chloride channel whose failure causes cystic fibrosis
2006-03-01

CFTR chloride channels are encoded by the gene mutated in patients with cystic fibrosis. These channels belong to the superfamily of ABC transporter ATPases. ATP-driven conformational changes, which in other ABC proteins fuel uphill substrate transport across cellular membranes, in CFTR open ...

NASA Astrophysics Data System (ADS)

6
ABCG transporters and disease.
2011-05-01

ATP-binding cassette (ABC) transporters form a large family of transmembrane proteins that facilitate the transport of specific substrates across membranes in an ATP-dependent manner. Transported substrates include lipids, lipopolysaccharides, amino acids, peptides, proteins, inorganic ions, sugars and xenobiotics. ...

PubMed

7
Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance.
2011-04-14

Peroxisomes are indispensable organelles in higher eukaryotes. They are essential for a number of important metabolic pathways, including fatty acid ?- and ?-oxidation, and biosynthesis of etherphospholipids and bile acids. However, the peroxisomal membrane forms an impermeable barrier to these metabolites. Therefore, peroxisomes need specific transporter proteins to transfer ...

PubMed

8
An ABC Transporter Mutation Alters Root Exudation of Phytochemicals that Provoke an Overhaul of Natural Soil Microbiota.

It has been shown that Arabidopsis root exudates can support the fungal community in native soils but not in non-native soils and recent evidence demonstrates the involvement of ABC transporters in the root secretion of phytochemicals. In this paper we examined differences in the root exudate profil...

Technology Transfer Automated Retrieval System (TEKTRAN)

9
Chloride channelopathies.
2009-03-01

Channelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms. Impaired chloride transport can cause diseases as diverse as cystic fibrosis, myotonia, epilepsy, hyperekplexia, lysosomal storage disease, deafness, renal salt loss, kidney stones and osteopetrosis. These ...

PubMed

10
Emerging New Paradigms for ABCG Transporters
2009-01-22

Every cell is separated from its external environment by a lipid membrane. Survival depends on the regulated and selective transport of nutrients, waste products and regulatory molecules across these membranes, a process that is often mediated by integral membrane proteins. The largest and most diverse of these membrane transport systems is the ATP binding ...

PubMed Central

11
The Haemophilus influenzae hFbpABC Fe3+ Transporter: Analysis of the Membrane Permease and Development of a Gallium-Based Screen for Mutants?
2007-07-11

The obligate human pathogen Haemophilus influenzae utilizes a siderophore-independent (free) Fe3+ transport system to obtain this essential element from the host iron-binding protein transferrin. The hFbpABC transporter is a binding protein-dependent ABC transporter that ...

PubMed Central

12
Whole genome re-sequencing identifies a mutation in an ABC transporter (mdr2) in a Plasmodium chabaudi clone with altered susceptibility to antifolate drugs.
2010-09-19

In malaria parasites, mutations in two genes of folate biosynthesis encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) modify responses to antifolate therapies which target these enzymes. However, the involvement of other genes which modify the availability of exogenous folate, for example, has been proposed. Here, we used short-read whole-genome ...

PubMed

13
Whole genome re-sequencing identifies a mutation in an ABC transporter (mdr2) in a Plasmodium chabaudi clone with altered susceptibility to antifolate drugs?
2011-02-01

In malaria parasites, mutations in two genes of folate biosynthesis encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) modify responses to antifolate therapies which target these enzymes. However, the involvement of other genes which modify the availability of exogenous folate, for example, has been proposed. Here, we used short-read whole-genome ...

PubMed Central

14
An ABC transporter and a cytochrome P450 of Nectria haematococca MPVI are virulence factors on pea and are the major tolerance mechanisms to the phytoalexin pisatin.
2011-03-01

The fungal plant pathogen Nectria haematococca MPVI produces a cytochrome P450 that is responsible for detoxifying the phytoalexin pisatin, produced as a defense mechanism by its host, garden pea. In this study, we demonstrate that this fungus also produces a specific ATP-binding cassette (ABC) transporter, NhABC1, that enhances its ...

PubMed

15
Human ATP-binding cassette (ABC) transporter family.
2009-04-01

There exist four fundamentally different classes of membrane-bound transport proteins: ion channels; transporters; aquaporins; and ATP-powered pumps. ATP-binding cassette (ABC) transporters are an example of ATP-dependent pumps. ABC transporters are ubiquitous ...

PubMed

16
Human ATP-binding cassette (ABC) transporter family
2009-04-01

There exist four fundamentally different classes of membrane-bound transport proteins: ion channels; transporters; aquaporins; and ATP-powered pumps. ATP-binding cassette (ABC) transporters are an example of ATP-dependent pumps. ABC transporters are ubiquitous ...

PubMed Central

17
An ABC transporter mutation is correlated with insect resistance to Bacillus thuringiensis Cry1Ac toxin.
2010-12-16

Transgenic crops producing insecticidal toxins from Bacillus thuringiensis (Bt) are commercially successful in reducing pest damage, yet knowledge of resistance mechanisms that threaten their sustainability is incomplete. Insect resistance to the pore-forming Cry1Ac toxin is correlated with the loss of high-affinity, irreversible binding to the mid-gut membrane, but the genetic factors responsible ...

PubMed

18
An ABC Transporter Mutation Is Correlated with Insect Resistance to Bacillus thuringiensis Cry1Ac Toxin
2010-12-16

Transgenic crops producing insecticidal toxins from Bacillus thuringiensis (Bt) are commercially successful in reducing pest damage, yet knowledge of resistance mechanisms that threaten their sustainability is incomplete. Insect resistance to the pore-forming Cry1Ac toxin is correlated with the loss of high-affinity, irreversible binding to the mid-gut membrane, but the genetic factors responsible ...

PubMed Central

19
Structure and Function of ABC Transporters - Table 1: Clinically relevant and atypical ABC proteins
2007-04-01

Table 1. Clinically relevant and atypical ABC proteins Kenneth J. Linton. Structure and Function of ABC Transporters. Physiology 22: 122-130, 2007

NSDL National Science Digital Library

20
Effects of the L511P and D512G mutations on the Escherichia coli ABC transporter MsbA.
2011-03-08

MsbA is a member of the ABC transporter superfamily and is homologous to ABC transporters linked to multidrug resistance. The nucleotide binding domains (NBDs) of these proteins include conserved motifs that are involved in ATP binding, including conserved SALD residues (D-loop) that are diagnostic in identifying ...

PubMed

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21
The hFbpABC Transporter from Haemophilus influenzae Functions as a Binding-Protein-Dependent ABC Transporter with High Specificity and Affinity for Ferric Iron
2004-09-01

Pathogenic Haemophilus influenzae, Neisseria spp. (Neisseria gonorrhoeae and N. meningitidis), Serratia marcescens, and other gram-negative bacteria utilize a periplasm-to-cytosol FbpABC iron transporter. In this study, we investigated the H. influenzae FbpABC transporter in a siderophore-deficient Escherichia coli ...

PubMed Central

22
A multidrug resistance transporter in Magnaporthe is required for host penetration and for survival during oxidative stress.
2006-12-22

In prokaryotes and eukaryotes, multidrug resistance (MDR) transporters use energy-dependent efflux action to regulate the intracellular levels of antibiotic or xenobiotic compounds. Using mutational analysis of ABC3, we define an important role for such MDR-based efflux during the host penetration step of Magnaporthe grisea ...

PubMed

23
Putative ABC Transporter Responsible for Acetic Acid Resistance in Acetobacter aceti
2006-01-01

Two-dimensional gel electrophoretic analysis of the membrane fraction of Acetobacter aceti revealed the presence of several proteins that were produced in response to acetic acid. A 60-kDa protein, named AatA, which was mostly induced by acetic acid, was prepared; aatA was cloned on the basis of its NH2-terminal amino acid sequence. AatA, consisting of 591 amino acids and ...

PubMed Central

24
A mutation of the H-loop selectively affects rhodamine transport by the yeast multidrug ABC transporter Pdr5
2008-04-01

The yeast ABC transporter Pdr5 plays a major role in drug resistance against a large number of structurally unrelated compounds. Although Pdr5 has been extensively studied, many important aspects regarding its molecular mechanisms remain unresolved. For example, a striking degeneration of conserved amino acid residues exists in the nucleotide binding ...

PubMed Central

25
The ABC of ABC-transport in the hyperthermophilic

). #12;Chapter 1 2.2. Binding protein dependent ABC- type transporters The sugar transporters characterized so, and Rad50cd, a DNA repair protein which shows ATP-binding domains similar to the domains found in ABC-transporters a binding protein-dependent ATP- binding cassette (ABC)-transporter ...

E-print Network

26
[Progress in the research on the ABCA gene family of vertebrates].
2006-08-01

The ATP-binding cassette (ABC) superfamily of genes encodes membrane proteins that transport many kinds of substrates across membranes. Based on amino acid sequence similarities and phylogeny, 48 ABC genes in the human genome were divided into seven subfamilies: ABCA to ABCG. Among them, ABCA transporters have a ...

PubMed

27
Mapping of Interdomain Interfaces Required for the Functional Architecture of Yor1p, a Eukaryotic ATP-binding Cassette (ABC) Transporter*S?
2008-09-26

ATP-binding cassette (ABC) transporters are a large superfamily of proteins that mediate substrate translocation across biological membranes. Our goal was to define the intramolecular interactions that contribute to quaternary assembly of a eukaryotic ABC transporter and determine how the architecture of this ...

PubMed Central

28
THE ROLE OF DELETERIOUS MUTATIONS IN ALLOPATRIC SPECIATION

... ABC � and A�B�C� � create a partial diploidy in the formerly haploid genome (or complete diploidy, in the case where the entire chromosomal compliment ... ...

NBII National Biological Information Infrastructure

29
The Twin Arginine Transport System Appears To Be Essential for Viability in Sinorhizobium meliloti?
2010-10-30

The twin arginine transport (Tat) system is responsible for transporting prefolded proteins to the periplasmic space. The Tat pathway has been implicated in many bacterial cellular functions, including motility, biofilm formation, and pathogenesis and symbiosis. Since the annotation of Sinorhizobium meliloti Rm1021 genome suggests that there may be up to ...

PubMed Central

30
Pharmacogenomics of human ABC transporters: detection of clinically important SNPs by SmartAmp2 method.
2011-04-01

Genetic polymorphisms and mutations in drug metabolizing enzymes, transporters, receptors, and other drug targets (e.g., toxicity targets) are linked to inter-individual differences in the efficacy and toxicity of many medications as well as risk of genetic diseases. Validation of clinically important genetic polymorphisms and the development of new ...

PubMed

31
An ABC Transporter of Streptococcus pneumoniae Involved in Susceptibility to Vancoresmycin and Bacitracin?
2009-05-09

Vancoresmycin is a novel tetramic acid antibiotic, probably interfering with functions of the cytoplasmic membrane. To investigate its mode of action, mutants of Streptococcus pneumoniae exhibiting reduced susceptibility to vancoresmycin were isolated at a low frequency. Four of them were further examined and showed similar pleiotropic phenotypes, including reduced growth rate, early autolysis, ...

PubMed Central

32
A new GntR family transcriptional regulator in streptomyces coelicolor is required for morphogenesis and antibiotic production and controls transcription of an ABC transporter in response to carbon source.
2006-08-25

We recently reported the isolation and initial characterization of a transposon-generated mutation that resulted in defects in both morphogenesis and antibiotic production in Streptomyces coelicolor. The insertion identified the SCO7168 open reading frame whose predicted product is a GntR family transcriptional regulator. Here, we show that this gene acts to repress ...

PubMed

33
A New GntR Family Transcriptional Regulator in Streptomyces coelicolor Is Required for Morphogenesis and Antibiotic Production and Controls Transcription of an ABC Transporter in Response to Carbon Source?
2006-11-25

We recently reported the isolation and initial characterization of a transposon-generated mutation that resulted in defects in both morphogenesis and antibiotic production in Streptomyces coelicolor. The insertion identified the SCO7168 open reading frame whose predicted product is a GntR family transcriptional regulator. Here, we show that this gene acts to repress ...

PubMed Central

34
Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains.
2010-11-01

The human ATP-binding cassette (ABC) transporter superfamily consists of 48 integral membrane proteins that couple the action of ATP binding and hydrolysis to the transport of diverse substrates across cellular membranes. Defects in 18 transporters have been implicated in human disease. In hundreds of cases, ...

PubMed

35
Chapter 6 Summary and concluding

-binding proteins (SBPs) of ATP Binding Cassette (ABC) transporters has been ongoing for at least four decades. Our on the lactococcal oligopeptide binding protein A (OppA), the receptor component of the ABC-transporter oligopeptide picture how these proteins work. Three types of ABC-transporters exist: ...

E-print Network

36
Mutation of GOGAT prevents pea bacteroid formation and N2 fixation by globally downregulating transport of organic nitrogen sources.
2011-02-23

Mutation of gltB (encoding glutamate oxoglutarate amidotransferase or GOGAT) in RU2307 increased the intracellular Gln:Glu ratio and inhibited amino acid transport via Aap and Bra. The mechanism probably involves global post-translational inhibition independent of Ntr. Transport was separately restored by increased gene expression of ...

PubMed

37
Conserved intramolecular disulfide bond is critical to trafficking and fate of ATP-binding cassette (ABC) transporters ABCB6 and sulfonylurea receptor 1 (SUR1)/ABCC8.
2011-01-03

The ATP-binding cassette (ABC) transporter ABCB6 is a mitochondrial porphyrin transporter that activates porphyrin biosynthesis. ABCB6 lacks a canonical mitochondrial targeting sequence but reportedly traffics to other cellular compartments such as the plasma membrane. How ABCB6 reaches these destinations is unknown. In this study, we ...

PubMed

38
The ATP-Binding Cassette Transporter ABCA4: Structural and Functional Properties and Role in Retinal Disease
2010-01-01

ATP-binding cassette transporters (ABC transporters) utilize the energy of ATP hydrolysis to translocate an unusually diverse set of substrates across cellular membranes. ABCA4, also known as ABCR, is a ~250 kDa single-chain ABC transporter localized to the disk margins of vertebrate ...

PubMed Central

39
The Signaling Interface of the Yeast Multidrug Transporter Pdr5 Adopts a Cis Conformation and There Is Functional Overlap and Equivalence of the Deviant and Canonical Q-loop Residues�
2010-06-01

ABC transporters are polytopic proteins. ATP hydrolysis and substrate transport take place in separate domains, and these activities must be coordinated through a signal interface. We previously characterized a mutation (S558Y) in the yeast multidrug transporter Pdr5 that uncouples ATP ...

PubMed Central

40
Chapter 1 General introduction to

of SBP-dependent membrane proteins. A-B: visualizes ABC- transporters. A: ABC-importer with the SBP dependent transport proteins ABC-transporters exist in all three kingdom of life and transport a large of the membrane protein. In mGluR this signal is triggered by ligand ...

E-print Network

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Separating the roles of acropetal and basipetal auxin transport on gravitropism with mutations in two Arabidopsis multidrug resistance-like ABC transporter genes.
2007-06-08

Two Arabidopsis thaliana ABC transporter genes linked to auxin transport by various previous results were studied in a reverse-genetic fashion. Mutations in Multidrug Resistance-Like1 (MDR1) reduced acropetal auxin transport in roots by 80% without affecting basipetal ...

PubMed

42
Antimony resistance during Visceral Leishmaniasis: A possible consequence of serial mutations in ABC transporters of Leishmania species.
2011-04-22

Visceral Leishmaniasis is a macrophage associated disorder for the treatment of which antimony based drugs like SAG and SSG were the first choice in the recent past. The clinical value of antimony therapy is now declined against VL because increasing cases of Sodium Antimony Gluconate (SAG) resistance have reached outstanding proportion in Bihar, India. Within this context we looked into the ...

PubMed

43
Antimony resistance during Visceral Leishmaniasis: A possible consequence of serial mutations in ABC transporters of Leishmania species
2011-04-22

Visceral Leishmaniasis is a macrophage associated disorder for the treatment of which antimony based drugs like SAG and SSG were the first choice in the recent past. The clinical value of antimony therapy is now declined against VL because increasing cases of Sodium Antimony Gluconate (SAG) resistance have reached outstanding proportion in Bihar, India. Within this context we looked into the ...

PubMed Central

44
Interaction potential of etravirine with drug transporters assessed in vitro.
2010-12-28

Etravirine is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infections. ABC transporters potentially mediate clinically relevant drug-drug interactions. We assessed substrate characteristics and the inhibitory and inductive potential of etravirine on ABC transporters. ...

PubMed

45
Residues responsible for the asymmetric function of the nucleotide binding domains of multidrug resistance protein 1.
2008-12-30

The two nucleotide binding domains (NBDs) of ATP binding cassette (ABC) transporters dimerize to form composite nucleotide binding sites (NBSs) each containing Walker A and B motifs from one domain and the ABC "C" signature from the other. In many ABC proteins, the NBSs are thought to be functionally equivalent. ...

PubMed

46
Structure and Function of ABC Transporters - Figure 1: The minimal ABC transporter has four domains
2007-04-01

FIGURE 1. The minimal ABC transporter has four domains. Two transmembrane domains (TMDs) bind ligand, and transport is driven by ATP binding and hydrolysis by the two nucleotide binding domains (NBDs). The TMDs from different subfamilies of ABC transporters are not necessarily homologous. The ...

NSDL National Science Digital Library

47
Gene expression profiling of ABC transporters in dermal fibroblasts of pseudoxanthoma elasticum patients identifies new candidates involved in PXE pathogenesis.
2008-10-20

Mutations in the ABCC6 gene, encoding the multidrug resistance-associated protein 6 (MRP6), cause pseudoxanthoma elasticum (PXE). This heritable disorder leads to pathological alterations in connective tissues. The implication of MRP6 deficiency in PXE is still unknown. Moreover, nothing is known about a possible compensatory expression of other ATP binding-cassette ...

PubMed

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