Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ABC transporter”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2000

Identification and characterisation of a silkworm ABC transporter gene homologous to Drosophila white.

In the silkworm, Bombyx mori, many eye- and egg-colour mutations affecting the synthesis and accumulation of ommochrome pigments have been described. In order to understand the pigment precursor transporters involved, ABC transporter genes homologous to the Drosophila white gene were isolated from the silkworm. Reverse transcriptase-polymerase chain reactions (RT-PCR) using embryonic mRNA amplified three cDNA fragments, named Bmwh1, Bmwh2 and Bmwh3 that showed homology to the white gene. Since Bmwh3 shows the highest degree of sequence identity and a similar expression pattern to the Drosophila homologue, we characterised this gene further. A 2667-bp Bmwh3 cDNA isolated from an embryonic library has one ORF encoding a polypeptide of 687 amino acids. The predicted protein has one ATP-binding domain, six transmembrane-spanning segments and high similarity to the Drosophila WHITE protein. Southern analysis indicates that Bmwh3 is a single-copy gene. Polyadenylated Bmwh3 transcripts about 2.7 kb long were detected in eggs, Malpighian tubules and pupal heads, but not in testes, posterior silk glands or fat body cells. The level of Bmwh3 mRNA was reduced in w3 and w3ol mutants but normal in other egg- and eye-colour mutants, suggesting that Bmwh3 correspond to the w3 locus. Genetic analysis was used to map the cloned gene to chromosome 10.

ATP-Binding Cassette Transporters↗
PubMed1995

The ard1 gene from Streptomyces capreolus encodes a polypeptide of the ABC-transporters superfamily which confers resistance to the aminonucleoside antibiotic A201A.

A gene (ard1) encoding resistance to the aminonucleoside antibiotic A201A was cloned from Streptomyces capreolus NRRL 3817, the producing organism, and expressed in Streptomyces lividans. The gene ard1 induced antibiotic resistance that was highly specific for A201A. The nucleotide sequence of ard1 contains an open reading frame of 1677 bp. Transcription initiation was found to take place approximately 86 nucleotides preceding the ATG translation-initiation codon, indicating that ard1 is transcribed from its own promoter. The deduced protein sequence (Ard1, 558 amino acids) presents two ATP-binding domains with significant similarities to those of the ATP-binding cassette transporters (ABC-transporters) superfamily, including some that confer drug resistance in a variety of antibiotic-producing Streptomyces, other Gram-positive bacteria and eukaryotic cells. As is probably the case for most of these proteins, the mechanism of A201A resistance conferred by Ard1 is an active efflux energized by ATP hydrolysis.

ATP-Binding Cassette Transporters↗
PubMed1993

ABC transporters: bacterial exporters.

The ABC transporters (also called traffic ATPases) make up a large superfamily of proteins which share a common function and a common ATP-binding domain. ABC transporters are classified into three major groups: bacterial importers (the periplasmic permeases), eukaryotic transporters, and bacterial exporters. We present a comprehensive review of the bacterial ABC exporter group, which currently includes over 40 systems. The bacterial ABC exporter systems are functionally subdivided on the basis of the type of substrate that each translocates. We describe three main groups: protein exporters, peptide exporters, and systems that transport nonprotein substrates. Prototype exporters from each group are described in detail to illustrate our current understanding of this protein family. The prototype systems include the alpha-hemolysin, colicin V, and capsular polysaccharide exporters from Escherichia coli, the protease exporter from Erwinia chrysanthemi, and the glucan exporters from Agrobacterium tumefaciens and Rhizobium meliloti. Phylogenetic analysis of the ATP-binding domains from 29 bacterial ABC exporters indicates that the bacterial ABC exporters can be divided into two primary branches. One branch contains the transport systems where the ATP-binding domain and the membrane-spanning domain are present on the same polypeptide, and the other branch contains the systems where these domains are found on separate polypeptides. Differences in substrate specificity do not correlate with evolutionary relatedness. A complete survey of the known and putative bacterial ABC exporters is included at the end of the review.

Amino Acid Sequence↗
PubMed1998

A comparative analysis of ABC transporters in complete microbial genomes.

The ABC transporter is a major class of cellular translocation machinery in all bacterial species encoded in the largest set of paralogous genes. The operon structure is frequently found for the genes of three molecular components: the ATP-binding protein, the membrane protein, and the substrate-binding protein. Here, we developed an "ortholog group table" by comparison and classification of known and putative ABC transporters in the complete genomes of seven microorganisms. Our procedure was to first search and classify the most conserved ATP-binding protein components by the sequence similarity and then to classify the entire transporter units by examining the similarity of the other components and the conservation of the operon structure. The resulting 25 ortholog groups of ABC transporters were well correlated with known functions. Through the analysis, we could assign substrate specificity to hypothetical transporters, predict additional transporter operons, and identify novel types of putative transporters. The ortholog group table was also used as a reference data set for functional assignment in four additional genomes. In general, the ABC transporter operons were strongly conserved despite the extensive shuffling of gene locations in bacterial evolution. In Synechocystis, however, the tendency of forming operons was clearly diminished. Our result suggests that the ancestral ABC transporter operons may have arisen early in evolution before the speciation of bacteria and archaea.

ATP-Binding Cassette Transporters↗
PubMed2005

Lipopolysaccharide stabilizes the crystal packing of the ABC transporter MsbA.

The ABC transporter MsbA is an integral membrane protein involved in the transport of lipid A and lipopolysaccharides to the outer leaflet of the inner membrane in bacteria. Here, the critical role of the natural substrate lipopolysaccharide in the crystallization and diffraction quality of MsbA crystals is reported. Initial crystals grown in complex with ATP-vanadate alone diffracted to approximately 9 A. Screening of the natural substrate lipopolysaccharides led to the crystallization of MsbA in complex with ADP-vanadate and Ra lipopolysaccharide. The increased order within the crystal lattice allowed structure determination to 4.2 A.

ATP-Binding Cassette Transporters↗
PubMed2006

Organization and function of the plant pleiotropic drug resistance ABC transporter family.

Among the ABC transporters, the pleiotropic drug resistance (PDR) family is particular in that its members are found only in fungi and plants and have a reverse domain organization, i.e., the nucleotide binding domain precedes the transmembrane domain. In Arabidopsis and rice, for which the full genome has been sequenced, the family of plant ABC transporters contains 15 and 23 PDR genes, respectively, which can be tentatively organized using the sequence data into five subfamilies. Most of the plant PDR genes so far characterized belong to subfamily I and have been shown to be involved in responses to abiotic and biotic stress, in the latter case, probably by transporting antimicrobial secondary metabolites to the cell surface. Only a single subfamily II member has been characterized. Induction of its expression by iron deficiency suggests its involvement in iron deficiency stress, thus, enlightening a new physiological role for a PDR gene.

ATP-Binding Cassette Transporters↗
PubMed2002

The E. coli BtuCD structure: a framework for ABC transporter architecture and mechanism.

The ABC transporters are ubiquitous membrane proteins that couple adenosine triphosphate (ATP) hydrolysis to the translocation of diverse substrates across cell membranes. Clinically relevant examples are associated with cystic fibrosis and with multidrug resistance of pathogenic bacteria and cancer cells. Here, we report the crystal structure at 3.2 angstrom resolution of the Escherichia coli BtuCD protein, an ABC transporter mediating vitamin B12 uptake. The two ATP-binding cassettes (BtuD) are in close contact with each other, as are the two membrane-spanning subunits (BtuC); this arrangement is distinct from that observed for the E. coli lipid flippase MsbA. The BtuC subunits provide 20 transmembrane helices grouped around a translocation pathway that is closed to the cytoplasm by a gate region whereas the dimer arrangement of the BtuD subunits resembles the ATP-bound form of the Rad50 DNA repair enzyme. A prominent cytoplasmic loop of BtuC forms the contact region with the ATP-binding cassette and appears to represent a conserved motif among the ABC transporters.

ATP-Binding Cassette Transporters↗
PubMed2000

ABC transporters in cellular lipid trafficking.

ATP-binding cassette (ABC) transporters constitute a group of evolutionary highly conserved cellular transmembrane transport proteins. Recent work has implicated ABC transporters in cellular transmembrane lipid transport and hereditary diseases have been causatively linked to defective ABC transporters translocating lipid compounds. The emerging concept that a defined subset of ABC transporters is intimately involved in cellular lipid trafficking has recently been substantiated convincingly by the finding that ABCA1 plays a central role in the regulation of HDL metabolism and macrophage targeting to the RES or the vascular wall. Differentiation dependent expression of a large number of ABC transporters in monocytes/macrophages and their regulation by sterol flux render these transporter molecules potentially critical players in atherogenesis and other chronic inflammatory diseases.

ATP Binding Cassette Transporter 1↗
PubMed2003

Crystal structure of the nucleotide-binding domain of the ABC-transporter haemolysin B: identification of a variable region within ABC helical domains.

The ABC-transporter haemolysin B is a central component of the secretion machinery that translocates the toxin, haemolysin A, in a Sec-independent fashion across both membranes of E. coli. Here, we report the X-ray crystal structure of the nucleotide-binding domain (NBD) of HlyB. The molecule shares the common overall architecture of ABC-transporter NBDs. However, the last three residues of the Walker A motif adopt a 3(10) helical conformation, stabilized by a bound anion. In consequence, this results in an unusual interaction between the Walker A lysine residue and the Walker B glutamate residue. As these residues are normally required to be available for ATP binding, for catalysis and for dimer formation of ABC domains, we suggest that this conformation may represent a latent monomeric form of the NBD. Surprisingly, comparison of available NBD structures revealed a structurally diverse region (SDR) of about 30 residues within the helical arm II domain, unique to each of the eight NBDs analyzed. As this region interacts with the transmembrane part of ABC-transporters, the SDR helps to explain the selectivity and/or targeting of different NBDs to their cognate transmembrane domains.

ATP-Binding Cassette Transporters↗
PubMed2005

ATP-binding cassette (ABC) transporters in normal and pathological lung.

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases.

ATP-Binding Cassette Transporters↗
PubMed2002

Structure and mechanism of ABC transporters.

ATP-binding cassette (ABC) transporters are central to many physiological processes, including the uptake of nutrients, the non-classical secretion of signaling molecules and toxins, multidrug resistance and the development of human disease. As one might expect from this spectrum of translocation events, these ubiquitous, ATP-dependent pumps or channels are capable of transporting an enormous variety of substrates, ranging from small ions to large proteins. Recently determined structures of full-length ABC transporters and isolated ABC domains have increased our understanding of the functional mechanism of these proteins.

ATP-Binding Cassette Transporters↗
PubMed2001

Mammalian ABC transporters in health and disease.

The ATP-binding cassette (ABC) transporters are a family of large proteins in membranes and are able to transport a variety of compounds through membranes against steep concentration gradients at the cost of ATP hydrolysis. The available outline of the human genome contains 48 ABC genes; 16 of these have a known function and 14 are associated with a defined human disease. Major physiological functions of ABC transporters include the transport of lipids, bile salts, toxic compounds, and peptides for antigen presentation or other purposes. We review the functions of mammalian ABC transporters, emphasizing biochemical mechanisms and genetic defects. Our overview illustrates the importance of ABC transporters in human physiology, toxicology, pharmacology, and disease. We focus on three topics: (a) ABC transporters transporting drugs (xenotoxins) and drug conjugates. (b) Mammalian secretory epithelia using ABC transporters to excrete a large number of substances, sometimes against a steep concentration gradient. Several inborn errors in liver metabolism are due to mutations in one of the genes for these pumps; these are discussed. (c) A rapidly increasing number of ABC transporters are found to play a role in lipid transport. Defects in each of these transporters are involved in human inborn or acquired diseases.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Overview: ABC transporters and human disease.

ABC transporters are found in all known organisms, and approximately 1,100 different transporters belonging to this family have been described in the literature. The family is defined by homology within the ATP-binding cassette (ABC) region, which extends outside of the more typical Walker motifs found in all ATP-binding proteins. Most family members also contain transmembrane domains involved in recognition of substrates, which are transported across, into, and out of cell membranes, but some members utilize ABCs as engines to regulate ion channels. There are approximately 50 known ABC transporters in the human, and there are currently 13 genetic diseases associated with defects in 14 of these transporters. The most common genetic disease conditions include cystic fibrosis, Stargardt disease, age-related macular degeneration, adrenoleukodystrophy, Tangier disease, Dubin-Johnson syndrome and progressive familial intrahepatic cholestasis. At least 8 members of this family are involved in the transport of a variety of amphipathic compounds, including anticancer drugs, and some appear to contribute to the resistance of cancer cells to chemotherapy.

ATP-Binding Cassette Transporters↗
PubMed2004

Structure and mechanism of ABC transporters.

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substrates across cell or organelle membranes. The recently determined crystal structures of the vitamin B(12) importer BtuCD and its cognate binding protein BtuF have revealed critical architectural features that are probably shared by other ABC transporters. For example, the arrangement of the ABC domains and their interface with the membrane-spanning domains are probably conserved, whereas the number of transmembrane helices and their arrangement are not. Two distinct mechanistic schemes for how ABC engines couple ATP hydrolysis to substrate transport have been proposed recently and are being explored.

ATP-Binding Cassette Transporters↗
PubMed2005

Transmembrane inhibitors of P-glycoprotein, an ABC transporter.

Drug resistance mediated by ABC transporters such as P-glycoprotein (P-gp) continues to be a major impediment to effective cancer chemotherapy. We have developed a panel of highly specific peptide inhibitors of P-gp based on the structure of the transmembrane domains of the transporter. These peptides are thought to exert their inhibitory action by disrupting the proper assembly of P-gp. A novel 96-well-plate assay based on the efflux of fluorescent P-gp substrate DiOC2 (3-ethyl-2-[3-(3-ethyl-2(3H)-benzoxazolylidene)-1-propenyl]benzoxazolium iodide) was developed and used for structure-functional characterization of transporter inhibitors. The studies strongly suggest that potent and selective inhibitors of ABC transporters can now be developed solely on the basis of the primary structures of the target proteins. The inhibition of P-gp with transmembrane peptides was shown to be chirality-independent. A 25-residue long retroinverso D-analogue of transmembrane domain 5 inhibited the efflux of the fluorescent P-gp substrate with an IC50 of 500 nM. Transmembrane peptides effectively sensitized resistant cancer cells to doxorubicin in vitro without demonstrating any cell toxicity of their own. The newly synthesized P-gp antagonists appear to be promising nontoxic drug resistance inhibitors that merit further development.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Identification of three ABC transporter genes in Trypanosoma brucei spp.

ABC transporters are key players in the multidrug resistance of cancer cells and yeast, and they appear to be involved in the drug resistance of various pathogenic protozoa. No member of this ubiquitous protein family has yet been described in Trypanosoma brucei spp., the causative agents of African sleeping sickness and animal trypanosomiases. However, different cases of artificially induced drug resistance were shown to be linked to a reduction in net drug uptake. We used polymerase chain reaction with degenerate oligonucleotide primers corresponding to particularly conserved regions within the ATP-binding cassette to probe the genome of T. brucei spp. for the presence of ABC transporter genes. Three different sequence segments encoding ATP-binding cassettes were identified, which, upon Southern blotting, appeared to belong to distinct genes designated Tbabc1, Tbabc2, and Tbabc3. They appear to be single-copy genes in both drug-susceptible and drug-resistant stocks of T. brucei spp., expressed in bloodstream forms as well as in the procyclic life stage. Whereas Tbabc3 shows moderate homology to various known ABC transporters, Tbabc1 and Tbabc2 are highly homologous to P-glycoprotein A of Leishmania tarentolae and to the multidrug resistance protein 1 of L. donovani, respectively.

ATP-Binding Cassette Transporters↗
PubMed2004

The role of ABC transporters in drug resistance, metabolism and toxicity.

ATP Binding Cassette (ABC) transporters form a special family of membrane proteins, characterized by homologous ATP-binding, and large, multispanning transmembrane domains. Several members of this family are primary active transporters, which significantly modulate the absorption, metabolism, cellular effectivity and toxicity of pharmacological agents. This review provides a general overview of the human ABC transporters, their expression, localization and basic mechanism of action. Then we shortly deal with the human ABC transporters as targets of therapeutic interventions in medicine, including cancer drug resistance, lipid and other metabolic disorders, and even gene therapy applications. We place a special emphasis on the three major groups of ABC transporters involved in cancer multidrug resistance (MDR). These are the classical P-glycoprotein (MDR1, ABCB1), the multidrug resistance associated proteins (MRPs, in the ABCC subfamily), and the ABCG2 protein, an ABC half-transporter. All these proteins catalyze an ATP-dependent active transport of chemically unrelated compounds, including anticancer drugs. MDR1 (P-glycoprotein) and ABCG2 preferentially extrude large hydrophobic, positively charged molecules, while the members of the MRP family can extrude both hydrophobic uncharged molecules and water-soluble anionic compounds. Based on the physiological expression and role of these transporters, we provide examples for their role in Absorption-Distribution-Metabolism-Excretion (ADME) and toxicology, and describe several basic assays which can be applied for screening drug interactions with ABC transporters in the course of drug research and development.

ATP-Binding Cassette Transporters↗
PubMed2004

Dynamics of ATP-binding cassette contribute to allosteric control, nucleotide binding and energy transduction in ABC transporters.

ATP-binding cassette (ABC) transporters move solutes across membranes and are associated with important diseases, including cystic fibrosis and multi-drug resistance. These molecular machines are energized by their charateristic ABC modules, molecular engines fuelled by ATP hydrolysis. A solution NMR study of a model ABC, Methanococcus jannaschii protein MJ1267, reveals that ADP-Mg binding alters the flexibilities of key ABC motifs and induces allosteric changes in conformational dynamics in the LivG insert, over 30A away from the ATPase active site. (15)N spin relaxation data support a "selected-fit" model for nucleotide binding. Transitions between rigidity and flexibility in key motifs during the ATP hydrolysis cycle may be crucial to mechanochemical energy transduction in ABC transporters. The restriction of correlated protein motions is likely a central mechanism for allosteric communications. Comparison between dynamics data from NMR and X-ray crystallography reveals their overall consistency and complementarity.

ATP-Binding Cassette Transporters↗