function, ABC transporters are composed of two hydrophobic transmembrane domains (TMDs) and two #Both multidrug transporter. #12;Chapter 2 12 Transmembrane domains The TMDs are two highly hydrophobic proteins transporter mutants that function in the absence of SBPs (see section `Transmembrane ...
E-print Network
Multidrug resistance mediated by P-glycoprotein and related ATP- binding cassette (ABC) transporters is an impediment to successful cancer therapy. Here we have examined for the first time the expression of the novel ABCB5 transporter in human physiologic...
National Technical Information Service (NTIS)
One of the major problems related with anticancer chemotherapy is resistance against anticancer drugs. The ATP-binding cassette (ABC) transporters are a family of transporter proteins that are responsible for drug resistance and a low bioavailability of drugs by pumping a variety of drugs out cells at the expense of ATP hydrolysis. One ...
PubMed Central
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
... is a member of the ABC (ATP-binding cassette) superfamily of transporters which also includes the cystic fibrosis transmembrane conductance ...
DTIC Science & Technology
Overexpression of ATP-binding cassette (ABC) drug transporters that actively efflux a variety of amphipathic compounds can cause multidrug resistance (MDR) in cancer cells, which is a major obstacle in the success of cancer chemotherapy. The development of synthetic small molecule compounds or the identification of natural products ...
Name: Ambudkar, Suresh V., Ph.D. Title: Senior Investigator; Chief, Transport Biochemistry Section, Laboratory of Cell Biology, CCR, National Cancer Institute, NIH Field: Biochemical Aspects of ABC transporters, multidrug resistance in cancer, and biochemistry
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
Divergent signature motifs of nucleotide binding domains of ABC multidrug transporter, CaCdr1p of pathogenic Candida albicans, are functionally asymmetric and noninterchangeable. Biochimica et biophysica acta. 2010.
Thirteen derivatives of the Streptococcus pneumoniae TIGR4 strain in which putative drug efflux pumps were genetically inactivated were constructed and characterized. The results indicate that two linked genes encoding the ABC-type transporters SP2073 and SP2075 function together to confer intrinsic resistance to a series of structurally unrelated ...
Multidrug resistance (MDR) is one of the most common complex phenomenons exhibited by cancer cells. It is a very common property of melanoma postchemotherapy. MDR transporters, ATP binding cassette (ABC) transporters, play a critical role in conferring this property to melanoma cells. miRNA are post-transcriptional ...
Some ABC transporters play a significant role in human health and illness because they confer multidrug resistance (MDR) through their overexpression. Compounds that inhibit the drug efflux mechanism can improve efficacy or reverse resistance. Of the eight described ABC transporter subfamilies, ...
Multi-drug resistance (MDR) of cancer cells severely limits therapeutic outcomes. A proposed mechanism for MDR involves the efflux of anti-cancer drugs from cancer cells, primarily mediated by ATP-binding cassette (ABC) membrane transporters including P-glycoprotein. This article reviews the recent progress of using active ingredients, ...
An underlying mechanism for multi drug resistance (MDR) is up-regulation of the transmembrane ATP-binding cassette (ABC) transporter proteins. ABC transporters also determine the general fate and effect of pharmaceutical agents in the body. The three major types of ABC ...
Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs ...
AbstractThe development of multidrug resistance to cancer chemotherapy is a major obstacle to the effective treatment of human malignancies. It has been established that membrane proteins, notably multidrug resistance (MDR), multidrug resistance protein (MRP), and breast cancer resistance protein (BCRP) of the ATP binding cassette ...
Some ATP-binding cassette (ABC) transporters of subfamilies B, C and G confer resistance to xenobiotics including insecticides. We identified genes of these subfamilies expressed by the lepidopterans Trichoplusia ni and Bombyx mori. The B. mori genome includes eight, six and 13 ABC-B, -C and -G genes, respectively, which encode ...
AbstractCmeABC, a multidrug efflux system in Campylobacter jejuni, plays an important role in the resistance to different antimicrobials and toxic compounds. Although this efflux system has been well characterized in C. jejuni and to a less extent in C. coli, it is unknown if CmeABC homologs are functional in other Campylobacter spp. ...
BackgroundThe large gene superfamily of ABC (ATP-binding cassette) transporters encodes membrane proteins involved in trafficking processes across biological membranes and further essential cell biological functions. ABC transporters are evolutionary ancient and involved in the biochemical defence against ...
Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches have been developed such as biochemotherapy and immunotherapy. The most common cause of multidrug resistance (MDR) in human cancers is the expression and function of one or more ATP-binding cassette (ABC) ...
In the present study, the gene expression of three multidrug resistance (MDR) and resistance-associated protein (MRP) transport proteins or efflux pumps was characterized and the phenotypic evidence for such pumps was demonstrated in cultured Madin-Darby canine kidney (MDCK) cells. A gradient for the fluorescent probe calcein was established between ...
BackgroundThe superfamily of ABC proteins is among the largest known in nature. Its members are mainly, but not exclusively, involved in the transport of a broad range of substrates across biological membranes. Many contribute to multidrug resistance in microbial pathogens and cancer cells. The diversity of ABC ...
ATP-binding cassette (ABC) transporters belong to one of the largest protein families that either import or export a wide spectrum of different substrates. Certain members of this superfamily have been implicated in multidrug resistance in various types of cancer as well as in pathogenic microorganisms. The role of ...
ATP-binding cassette (ABC) transporters are drug efflux pumps responsible for the multidrug resistance phenotype causing hepatocellular carcinoma (HCC) treatment failure. Here we studied the expression of 15 ABC transporters relevant for multidrug resistance in 19 paired ...
Multidrug resistance (MDR) mediated by MDR1 (ABCB1) P-glycoprotein and related ATP-binding cassette (ABC) transporters is an impediment to successful cancer therapy. ABCB5 P-glycoprotein is a novel ABC transporter, which mediates drug efflux in cancer cells and regulates cell fusion and ...
Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette ...
The ATP-binding cassette (ABC) class of proteins is one of the most functionally diverse transporter families found in biological systems. Although the abundance of ABC proteins varies between species, they are highly conserved in sequence and often demonstrate similar functions across prokaryotic and eukaryotic organisms. Beginning ...
. B. (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P proteins as fundamental transporters of metabolic and xenobiotic organic cations, Trends Pharmacol. Sci. 27-deficient Streptococcus pneumoniae strain panel to identify ABC-class multidrug transporters ...
ATP binding cassette (ABC) transporters are increasingly recognized for their ability to modulate the absorption, distribution, metabolism, secretion and toxicity of xenobiotics. In addition to their essential function in drug resistance, there is also emerging evidence documenting the important role ABC ...
About seven million people die of cancer every year. This is largely due to development of drug resistance, particularly multidrug resistance, in the tumor cells. Multidrug resistance (MDR) arises due to over-expression of MDR proteins in the cancer cells, which cause efflux of anticancer drugs from the cells using ATP. MDR proteins are members of the ...
ABC transporters (also known as traffic ATPases) form a large family of proteins responsible for the translocation of a variety of compounds across membranes of both prokaryotes and eukaryotes. The recently completed Escherichia coli genome sequence revealed that the largest family of paralogous E. coli proteins is composed of ABC ...
Adenosine triphosphate-binding cassette (ABC) transporters, such as P-glycoprotein (Pgp, ABCB1), breast cancer resistance protein (BCRP, ABCG2) and multidrug resistance-associated proteins (MRPs) are expressed in high concentrations at various physiological barriers (e.g. blood-brain barrier, blood-testis barrier, blood-tumor barrier), ...
A single-copy gene, designated TruMDR2, encoding an ATP-binding cassette (ABC) transporter was cloned and sequenced from the dermatophyte Trichophyton rubrum. The ORF of TruMDR2 was 4048 nt and the deduced amino acid sequence showed high homology with ABC transporters involved in drug efflux in other fungi. The ...
One way to combat multidrug-resistant microorganisms is the use of efflux pump inhibitors (EPIs). Spontaneous mutants resistant to the EPI reserpine selected from Streptococcus pneumoniae NCTC 7465 and R6 at a frequency suggestive of a single mutational event were also multidrug resistant. No mutations in pmrA (which encodes the efflux protein PmrA) were ...
Receptor-mediated endocytosis plays important role in the selective uptake of proteins at the plasma membrane of eukaryotic cells. Endocytosis regulates many processes of cell signalling by controlling the number of functional receptors on the cell surface. The article reviews the mechanism of clathrin-dependent endocytosis and the possibility of using this phenomenon for the targeted delivery of ...
LmrA from Lactococcus lactis is a multidrug transporter and a member of the ATP binding cassette (ABC) transporter family. ABC transporters consist of a transmembrane domain (TMD) and a nucleotide binding domain (NBD). The NBD contains the highly conserved signature motifs ...
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 ...
Overexpression of the CaCDR1-encoded multidrug efflux pump protein CaCdr1p (Candida drug resistance protein 1), belonging to the ATP binding cassette (ABC) superfamily of transporters, is one of the most prominent contributors of multidrug resistance (MDR) in Candida albicans. Thus, blocking or modulating the ...
Multidrug resistance protein 1 (MRP1/ABCC1) is a 190 kDa member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that is clinically relevant for its ability to confer multidrug resistance by actively effluxing anticancer drugs. Knowledge of the atomic structure of MRP1 is needed to ...
Energy Citations Database
Active efflux is a common resistance mechanism in a wide range of bacterial pathogens. It is responsible for the transport of such toxic compounds as drugs, toxins, and detergents. Pumps with broad substrate profiles promote the emergence of multidrug-resistant bacterial pathogens that are a particular threat to contemporary medicine, such as Pseudomonas ...
Human multidrug resistance ABC transporters are ubiquitous membrane proteins responsible for the efflux of multiple, endogenous or exogenous, compounds out of the cells, and therefore they are involved in multi-drug resistance phenotype (MDR). They thus deeply impact the pharmacokinetic parameters and toxicity ...
Most Candida krusei strains are innately resistant to fluconazole (FLC) and can cause breakthrough candidemia in immunocompromised individuals receiving long-term prophylactic FLC treatment. Although the azole drug target, Erg11p, of C. krusei has a relatively low affinity for FLC, drug efflux pumps are also believed to be involved in its innate FLC resistance. We describe here the isolation and ...
The ATP-binding cassette (ABC) superfamily is the largest protein family identified in all organisms. It is a highly conserved domain responsible for the ATP-dependent transport of substances including ions, carbohydrates, xenobiotics, drugs, and peptides. Also, the subfamily, multidrug resistance...
Technology Transfer Automated Retrieval System (TEKTRAN)
Classical cytotoxic treatment of rhabdomyosarcoma (RMS) is often accompanied by significant morbidity and poor response. This cytotoxic therapy may induce a multidrug resistance (MDR) phenotype in RMS which is associated with decreased effectiveness of chemotherapy. The majority of MDR molecules belong to a family of ABC (ATP binding cassette) ...
Lactic acid bacteria play an essential role in many food fermentation processes. They are anaerobic organisms which obtain their metabolic energy by substrate phosphorylation. In addition three secondary energy transducing processes can contribute to the generation of a proton motive force: proton/substrate symport as in lactic acid excretion, electrogenic precursor/product exchange as in ...
BackgroundMany drugs of natural origin are hydrophobic and can pass through cell membranes. Hydrophobic molecules must be susceptible to active efflux systems if they are to be maintained at lower concentrations in cells than in their environment. Multi-drug resistance (MDR), often mediated by intrinsic membrane proteins that couple energy to drug efflux, provides this ...
ABC transporters are a large family of membrane proteins involved in a variety of cellular processes, including multidrug and tumor resistance and ion channel regulation. Advances in the structural and functional understanding of ABC transporters have revealed that hydrolysis at the two ...
In tumor cell lines, multidrug resistance is often associated with an ATP-dependent decrease in cellular drug accumulation which is attributed to the overexpression of certain ATP-binding cassette (ABC) transporter proteins. ABC proteins that confer drug resistance include (but are not limited to) P-glycoprotein ...
A mariner transposon bank was used to identify loci that contribute to the innate resistance of Listeria monocytogenes to the lantibiotic nisin. In addition to highlighting the importance of a number of loci previously associated with nisin resistance (mprF, virRS, and telA), a nisin-sensitive phenotype was associated with the disruption of anrB (lmo2115), a gene encoding the permease component of ...
ABC transporters are a large and important family of membrane proteins involved in substrate transport across the membrane. The transported substrates are quite diverse, ranging from monatomic ions to large biomolecules. Consequently, some ABC transporters are involved in ...
Puromycin, hygromycin, and geneticin (G418) are antibiotics frequently used to select genetically engineered eukaryotic cells after transfection or transduction. Because intrinsic or acquired high expression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (Pgp/ABCB1) and multidrug resistance-associated proteins ...
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anti-cancer drug and can develop by multiple mechanisms. These mechanisms can act individually or synergistically, leading to multidrug resistance (MDR), in which the cell becomes resistant to a ...
Resistance to chemotherapeutic agents remains one of the major impediments to a successful treatment of chronic myeloid leukemia (CML). Misregulation of the activity of a specific group of ATP-binding cassette transporters (ABC) is responsible for reducing the intracellular concentration of drugs in leukemic cells. Moreover, a consistent body of evidence ...
Resistance to cytotoxic drugs is a significant problem of systemic treatment of cancers. Apart from drug inactivation, changes in target enzymes and proteins, increased DNA repair and suppression of apoptosis, an important mechanism of resistance is an active drug efflux from cancer cells. Drug efflux across the cell membrane is caused by transport proteins such as ...
A DNA fragment responsible for resistance to antimicrobial agents was cloned from the chromosomal DNA of Enterococcus faecalis ATCC 29212 by using drug-hypersensitive mutant Escherichia coli KAM32 as a host cell. Cells of E. coli KAM32 harboring a recombinant plasmid (pAEF82) carrying the DNA fragment became resistant to many structurally unrelated antimicrobial agents, such as norfloxacin, ...
Members of the ATP-binding cassette (ABC) transporter superfamily exist in bacteria, fungi, plants, and animals and play key roles in the efflux of xenobiotic compounds, physiological substrates, and toxic intracellular metabolites. Based on sequence relatedness, mammalian ABC proteins have been divided into seven subfamilies, ...
Summary: Members of the ATP-binding cassette (ABC) transporter superfamily exist in bacteria, fungi, plants, and animals and play key roles in the efflux of xenobiotic compounds, physiological substrates, and toxic intracellular metabolites. Based on sequence relatedness, mammalian ABC proteins have been divided into seven subfamilies, ...
Lactobacillus brevis is a major contaminant of spoiled beer. The organism can grow in beer in spite of the presence of antibacterial hop compounds that give the beer a bitter taste. The hop resistance in L. brevis is, at least in part, dependent on the expression of the horA gene. The deduced amino acid sequence of HorA is 53% identical to that of LmrA, an ATP-binding cassette ...
In this study, we have explored the structure activity relationships of substrates of two major, promiscuous, multidrug transporters of an opportunistic human pathogen Candida albicans namely, CaCdr1p and CaMdr1p. To differentiate between substrates and non-substrates, the susceptibilities of the Saccharomyces cerevisiae strains over-expressing CaCdr1p or ...
Background and purpose:ABC multidrug transporters (MDR-ABC proteins) cause multiple drug resistance in cancer and may be involved in the decreased anti-cancer efficiency and modified pharmacological properties of novel specifically targeted agents. It has been documented that ABCB1 and ABCG2 interact with several ...
The multidrug resistant phenotype of cancer cells can often result from the over-production of a number of ATP binding cassette (ABC) transporters, including P-glycoprotein (P-gp). These multi-drug efflux transporters expel administered anti-cancer drugs from the cancer cell, preventing ...
ABC transporters export clinically-relevant drugs and their over-expression causes multidrug resistance. In order to knock-down ABC transporters, ABCC1 and ABCC2, 13 shRNAs were developed. Four shRNA candidates were tested in vivo using self-complementary adeno-associated virus serotype 8. A ...
Multidrug-resistance protein?1 (MRP1) belongs to the ATP-binding cassette (ABC) transporter family. MRP1 mediates MDR (multidrug resistance) by causing drug efflux either by conjugation to glutathione (GSH) or by co-transport with free GSH (without covalent bonding between the drug and GSH). We ...
The gene and protein expression and the cellular localization of the ABC transport proteins breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance-associated protein 2 (MRP2) have been examined in the intestines, liver and kidney in horse. High gene and ...
ATP-binding cassette (ABC) transporters are able to efflux their substrate drugs from the cells. We compared expression of efflux proteins in normal human corneal epithelial tissue, primary human corneal epithelial cells (HCEpiC), and corneal epithelial cell culture model (HCE model) based on human immortal cell line. Expression of ...
Drug resistance represents a serious barrier to the successful treatment of hematological malignancies. In leukemias, resistance mechanisms that involve membrane-resident proteins belonging to the ABC (ATP-binding cassette) transporter protein family are of particular interest, wherein enhanced expression is often associated with poor prognosis and ...
Bacterial ATP binding cassette (ABC) exporters fulfill a wide variety of transmembrane transport roles and are homologous to the human multidrug resistance P-glycoprotein. Recent x-ray structures of the exporters MsbA and Sav1866 have begun to describe the conformational changes that accompany the ABC ...
The ATP binding cassette (ABC) transporter LmrA from Lactococcus lactis transports cytotoxic molecules at the expense of ATP. Molecular and kinetic details of LmrA can be assessed by solid-state nuclear magnetic resonance (ssNMR), if functional reconstitution at a high protein-lipid ratio can be achieved and the kinetic rate constants ...
ATP-binding cassette (ABC) proteins play key role in tissue defence by transporting metabolic waste and toxic chemicals out of the cells. Consequently, intact cell systems are required to study xenobiotic interactions with ATP-dependent transporters. The aim of the present study was to set up an intestinal precision-cut slice technique ...
MgrA is a known regulator of the expression of several multidrug transporters in Staphylococcus aureus. We identified another regulator of multiple efflux pumps, NorG, by its ability, like that of MgrA, to bind specifically to the promoter of the gene encoding the NorA efflux pump. NorG is a member of the family of the GntR-like transcriptional regulators, ...
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, ...
Multidrug resistance (MDR) to anti-cancer drugs has been associated with the overexpression of P-glycoprotein (P-gp) and the multidrug resistance-associated protein (MRP), both being members of the ATP-binding cassette (ABC) superfamily of transporters. We investigated whether in addition to P-gp and MRP, another ...
ATP-binding cassette (ABC) transporters regulate the transport of a variety of physiologic substrates. Moreover, several human ABC proteins are responsible for drug exclusion in compound-treated tumor cells, providing cellular mechanisms for the development of multidrug resistance and, ...
The ABC transporter LmrA from Lactococcus lactis has been intensively studied and a role in multidrug resistance was proposed. Here, we performed a comprehensive detergent screen to analyze the impact of detergents for a successful solubilization, purification and retention of functional properties of this ABC ...
to an ABC-type multidrug transport protein from Aspergillus nidulans (E = 8 � 10�28 ), a phenylacetyl-CoA ligase from Aspergillus fumigatus (E = 9 � 10�54 ), and two hypothetical proteins 15 20 25 30 15 20 25 30 membrane protein Aspergillus fumigatus 2.00E�42 EAL88317 60sF ES408467 451 Cytochrome P450 monoxooxygenase
Cellular expression of ATP-binding cassette (ABC) transport proteins, such as P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), or ABCG2, is known to confer a drug-resistant phenotype. Thus, the development of effective transporter inhibitors could be of value to cancer treatment. CBT-1� is a ...
ATP-binding cassette (ABC) transporters are well known for their roles as multidrug resistance determinants but also play important roles in regulation of lipid levels. In the yeast Saccharomyces cerevisiae, the plasma membrane ABC transporter proteins Pdr5 and Yor1 are required for normal ...
In the search for heterologous activators for actinorhodin production in Streptomyces lividans, 3.4 kb of DNA from Streptomyces rochei F20 (a streptothricin producer) were characterized. Subcloning experiments showed that the minimal DNA fragment required for activation was 0.4 kb in size. The activation is mediated by increasing the levels of transcription of the actII-ORF4 gene. Sequencing of ...
... the ABC (or ATP-binding cassette) superfamily which also includes other important proteins such as the cystic fibrosis transmembrane conductance ...
ATP-driven efflux pumps such as phosphoglycoprotein-170 (P-gp), multidrug-resistance-associated protein-2 (MRP-2), or breast cancer resistance protein (BCRP) play a crucial role in limiting the efficacy of tumor pharmacotherapy. Selected flavonoids have been suggested to inhibit individual efflux-transporters and to act therefore as ...
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
Flavonoids with hydrophobic e.g. prenyl substituents might constitute the promising candidates for multidrug resistance (MDR) reversal agents. The interaction of 8-prenylnaringenin (8-isopentenylnaringenin), a potent phytoestrogen isolated from common hop (Humulus lupulus), with two multidrug resistance-associated ABC ...
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 ...
The human breast cancer resistance protein (BCRP/ABCG2) is the second member of the G subfamily of the large ATP-binding cassette (ABC) transporter superfamily. BCRP was initially discovered in multidrug resistant breast cancer cell lines where it confers resistance to chemotherapeutic agents such as mitoxantrone, topotecan and ...
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 ...
Nine proteins of the ABC superfamily (P-glycoprotein, 7 MRPs and BCRP) are involved in multidrug transport. Being localised at the surface of endothelial or epithelial cells, they expel drugs back to the external medium (if located at the apical side [P-glycoprotein, BCRP, MRP2, MRP4 in the kidney]) or to the blood (if located at the ...
ABC multidrug transporter proteins expel a wide variety of structurally unrelated, mostly hydrophobic compounds from cells. The special role of these transporters both at the physiological barriers and in cancer cells is based on their extremely broad substrate recognition. Since hydrophobic compounds are known to ...
We have taken advantage of the natural milieu of matched pair of azole sensitive (AS) and azole resistant (AR) clinical isolates of Candida glabrata for expressing its major ABC multidrug transporter, CgCdr1p for structure and functional analysis. This was accomplished by tagging a green fluorescent protein (GFP) downstream of ORF of ...
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 ...
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. ...
Previously published 3-D structures of a prototypic ATP-binding cassette (ABC) transporter, MsbA, have been recently corrected revealing large rigid-body motions possibly linked to its catalytic cycle. Here, a closely related multidrug bacterial ABC transporter, BmrA, was studied using ...
ATP-binding cassette (ABC) transporters constitute a large class of molecular pumps whose central role in chemotherapy resistance has highlighted their clinical relevance. We investigated whether the lipid composition of the membrane affects the function and structure of HorA, a bacterial ABC multidrug ...
ATP-binding cassette (ABC) systems translocate a wide range of solutes across cellular membranes. The thermophilic gram-negative eubacterium Thermus thermophilus, a model organism for structural genomics and systems biology, discloses ?46 ABC proteins, which are largely uncharacterized. Here, we functionally analyzed the first two and only ...
P-glycoprotein (Pgp; ABCB1), a member of the ATP-binding cassette (ABC) superfamily, exports structurally diverse hydrophobic compounds from the cell, driven by ATP hydrolysis. Pgp expression has been linked to the efflux of chemotherapeutic drugs in human cancers, leading to multidrug resistance (MDR). The protein also plays an important physiological ...
). #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 ...
The multidrug-resistant mutant Streptococcus pneumoniae M22 constitutively overexpresses two genes (patA and patB) that encode proteins homologous to known efflux proteins belonging to the ABC transporter family. It is shown here that PatA and PatB were strongly induced by quinolone antibiotics and distamycin in ...
Pregnant women are often complicated with diseases including viral or bacterial infections, epilepsy, hypertension, or pregnancy-induced conditions such as depression and gestational diabetes that require treatment with medication. In addition, substance abuse during pregnancy remains a major public health problem. Many drugs used by pregnant women are off label without the necessary dose, ...
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 ...
ABC transporter (ATP-binding-cassette transporter) proteins have been strongly associated with the phenomenon of multidrug resistance in cancer cells. Furthermore, their physiological expression has been studied in many organisms, including bacteria, fungi, plants and vertebrate or invertebrate animals. Their ...
