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| <StructureSection load='1l7v' size='400' side='right' scene='ABC_transporter/Cv/1' caption='Se-Met B12 Bacterial ABC Transporter complex with cyclo-tetrametavanadate, [[1l7v]]. Permease protein in green and grey, ATP-binding protein in yellow and pink.'> | | <StructureSection load='3tql' size='350' side='right' caption='Arginine ABC transporter complex with arginine (PDB code [[3tql]])' scene='42/429005/Cv/2'> |
| | | __TOC__ |
| '''A'''TP '''B'''inding '''C'''assette (ABC) '''[[Transporters]]''' are ATP-dependent membrane proteins critical for most aspects of cell physiology, including the uptake of nutrients (importers) and elimination of waste products and energy generation (exporters) which are predominantly expressed in excretory organs, such as the liver, intestine, blood-brain barrier, blood-testes barrier, placenta, and kidney<ref name="Kidney"/><ref name="FourDomainsABCT"/>. There are many ABC Transporters in organisms, for instance, there are 28 in yeast,58 in ''Caenorhabditis'', 51 in ''Drosophila'',129 in ''Arabadopsis'',and the 69 ABC transporters in ''E. coli'' account for almost 5% of its genomic coding capacity<ref name="EColi"/>. ABC transporter protein translocates substrates across membranes. It contains a Solute Binding Domain (SBD). CFTR (Cystic Fibrosis Transmembrane Regulator) translocates chloride and thiocyanate. It contains a nucleotide binding domain (NBD). Mutations in CFTR lead to Cystic Fibrosis. In humans the ABC transporters are classified into subfamilies, i.e. ABCB6 is ABC subfamily B member 6. The images at the left and at the right correspond to one representative ABC transporter, ''i.e.'' the crystal structure of B12 Bacterial ABC Transporter ([[1l7v]]).
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| == Function == | | == Function == |
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| ABC Transporters has two main functionality acting either as exporters or importers. '''ABC ''Exporters''''' release bound drugs to the extracellular environment, while '''ABC ''Importers''''' accept substrate molecules from their relevant substrate-binding proteins<ref name="biochembook"/>. For instance the Vitamin B12 transporter BtuCD (PDB [[1l7v]]) is a binding protein-dependent ABC transporter system that uses the power of ATP hydrolysis to pump vitamin B12 into the cytoplasm of E. coli<ref name="BtuCD-Ecoli"/>. | | '''ATP Binding Cassette''' (ABC) '''[[Transporters]]''' are ATP-dependent membrane proteins critical for most aspects of cell physiology, including the uptake of nutrients (importers) and elimination of waste products and energy generation (exporters) which are predominantly expressed in excretory organs, such as the liver, intestine, blood-brain barrier, blood-testes barrier, placenta, and kidney<ref name="Kidney"/><ref name="FourDomainsABCT"/>. There are many ABC Transporters in organisms, for instance, there are 28 in yeast, 58 in ''Caenorhabditis'', 51 in ''Drosophila'',129 in ''Arabadopsis'',and the 69 ABC transporters in ''E. coli'' account for almost 5% of its genomic coding capacity<ref name="EColi"/>. ABC transporter protein translocates substrates across membranes. It contains a Solute Binding Domain (SBD). '''CFTR''' (Cystic Fibrosis Transmembrane Regulator) translocates chloride and thiocyanate. It contains a nucleotide binding domain (NBD). In humans the ABC transporters are classified into subfamilies, i.e. ABCB6 is ABC subfamily B member 6. The '''Lipoprotein-release ABC transporter complex LolCDE''' is responsible for the transport of lipoproteins from the inner cell membrane to the outer membrane<ref>PMID:20149407</ref>.<br /> |
| | | ABC Transporters have two main functionalities acting either as exporters or importers. '''ABC ''Exporters''''' release bound drugs to the extracellular environment, while '''ABC ''Importers''''' accept substrate molecules from their relevant substrate-binding proteins<ref name="biochembook"/>. For instance the Vitamin B12 transporter BtuCD (PDB [[1l7v]]) is a binding protein-dependent ABC transporter system that uses the power of ATP hydrolysis to pump vitamin B12 into the cytoplasm of E. coli<ref name="BtuCD-Ecoli"/>. <br /> |
| '''ABC Exporters''' Use ATP to drive import and export functions providing multidrug resistance. In eukaryoles, for instance, ABC Transporters are problematic because they export therapeutic drugs such as those used in chemotherapy regimens, which must be changed frequently to avoid the rejection of the drugs<ref name="biochembook"/>. | | *For details of '''serotonin transporter''' see [[Serotonin Transporter]]<br /> |
| | *For details of '''sugar transporter''' see [[GLUT1]],[[Glut3]], [[Sanbox glut3]], [[Glucose transport protein]] and [[GLUT4]]<br /> |
| | *For details of '''urea transporter''' see [[Urea transporter]]<br /> |
| | *For details of '''Cystic fibrosis transmembrane conductance regulator (CFTR)''' see [[Cystic fibrosis transmembrane conductance regulator (CFTR)]] and [[CFTR (Hebrew)]]<br /> |
| | *For details on '''plant abc transporter''' see [[Rice abc transporter]]<br /> |
| | *For details on '''dipeptide abc transporter''' see [[Periplasmic dipeptide-binding protein]]<br /> |
| | *For details on '''oligopeptide abc transporter''' see [[Oligopeptide-binding protein]]<br /> |
| | *For details on '''ABCG2 multi drug transporter''' see [[ABCG2 multidrug transporter]]<br /> |
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| To achieve export, ABC transporters require a minimum of four domains. Two transmembrane domains (TMDs) form the ligand binding sites and provide specificity, and two NBDs bind and hydrolyze ATP to drive the trans-location of the bound ligand. The NBDs, but not the TMDs, are homologous throughout the family and have several characteristic motifs including the Walker A and B motifs common to many nucleotide binding proteins and others like the ABC signature, stacking aromatic D, H, and Q loops, which are unique to the family<ref name="FourDomainsABCT"/>.
| | == Structural highlights == |
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| | To achieve export, ABC transporters require a minimum of four domains. Two transmembrane domains (TMDs) form the ligand binding sites and provide specificity, and two NBDs bind and hydrolyze ATP to drive the trans-location of the bound ligand. The NBDs, but not the TMDs, are homologous throughout the family and have several characteristic motifs including the Walker A (GxxGxGKST) and B (ILLDEAT) motifs common to many nucleotide binding proteins and others like the ABC signature, stacking aromatic D, H, and Q loops, which are unique to the family<ref name="FourDomainsABCT"/>. |
| | *<scene name='42/429005/Cv/5'>Active site</scene> of Arginine ABC transporter complex with arginine (PDB code [[3tql]]). Water molecules are shown as red spheres. |
| == Disease == | | == Disease == |
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| There are currently 50 known ABC transporters in human. Of these there are 13 genetic diseases known to be associated with 14 of them. Among the diseases are cystic fibrosis, Stargardt disease, age-related macular degeneration and others. | | There are currently 50 known ABC transporters in human. Of these there are 13 genetic diseases known to be associated with 14 of them. Among the diseases are cystic fibrosis, Stargardt disease, age-related macular degeneration and others. Mutations in CFTR lead to Cystic Fibrosis. '''ABC Exporters''' use ATP to drive import and export functions providing multidrug resistance. In eukaryoles, for instance, ABC Transporters are problematic because they export therapeutic drugs such as those used in chemotherapy regimens, which must be changed frequently to avoid the rejection of the drugs<ref name="biochembook"/>. |
| </StructureSection> | |
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| == 3D Structures of ABC transporter == | | == 3D Structures of ABC transporter == |
| | [[ABC transporter 3D structures]] |
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
| | </StructureSection> |
| {{#tree:id=OrganizedByTopic|openlevels=0|
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| * ABC amino acids transporters
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| **Arginine ABC transporter
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| ***[[3g41]] - CpABC arginine transporter, soluble domain (mutant) – ''Chlamydia pneumoniae''<br />
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| ***[[3n26]] - CpABC arginine transporter, soluble domain<br />
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| ***[[3tql]] - CbABC arginine transporter + arginine – ''Coxiella burnetii''<br />
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| ***[[2q2a]] - GsABC amino acids transporter (mutant)+arginine - ''Geobacillus stearothermophilus''<br />
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| ***[[3del]] - ABC arginine transporter – ''Chlamydia trachomatis''<br />
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| ***[[4h5f]] - SpABC amino acid transporter + arginine - ''Streptococcus pneumoniae'' <br />
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| **Branched amino acid ABC transporter
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| ***[[3lkb]] - TtABC branched amino acids transporter (mutant)+valine – ''Thermus thermophilus''<br />
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| ***[[3h5l]] - SpABC branched-chain amino acids transporter<br />
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| ***[[1g9x]], [[1g6h]], [[1gaj]] - ABC branched-chain amino acids transporter – ''Methanocaldococcus jannaschii''<br />
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| ***[[3td9]] - TmABC branched-chain amino acids transporter + phenylalanine - ''Thermotoga maritima''<br />
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| ***[[3i09]], [[3n0w]] - ABC branched amino acids transporter – ''Burkholderia mallei''<br />
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| ***[[3ip7]] – AtABC valine transporter<br />
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| ***[[3ipc]] – AtABC leucine transporter<br />
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| **Lysine ABC transporter
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| ***[[3k4u]] - ABC transporter + lysine – ''Wolinella succinogenes''<br />
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| ***[[3i6v]] - SpABC amino acids transporter + lysine – ''Silicibacter pomeroyi''<br />
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| ***[[2pvu]] - GsABC amino acids transporter (mutant)+lysine<br />
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| **Histidine ABC transporter
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| ***[[2q2c]] - GsABC amino acids transporter (mutant)+histidine<br />
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| **Glutamine ABC transporter
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| ***[[4kpt]], [[4kr5]], [[4la9]] - LlABC glutamine transporter – ''Lactococcus lactis''<br />
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| ***[[4kqp]] - LlABC glutamine transporter + glutamine<br />
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| **Methionine ABC transporter
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| ***[[2qsw]] - EfABC methionine transporter C-terminal – ''Enterococcus faecalis''<br />
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| ***[[3ced]] - SaABC methionine transporter NIL domain - ''Staphylococcus aureus''<br />
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| ***[[3tqw]] - CbABC methionine transporter + methionine <br />
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| ***[[3dhw]] - EcABC methionine transporter<br />
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| ***[[3dhx]]- EcABC methionine transporter C2 domain<br />
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| ***[[2qrr]] - ABC methionine transporter soluble domain - ''Vibrio parahaemolyticus'' <br />
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| **Alanine ABC transporter
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| ***[[3ip5]], [[3ipa]] – AtABC alanine transporter – ''Agrobacterium tumefaciens''<br />
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| **Proline ABC transporter
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| ***[[3ip6]] – AtABC proline transporter<br />
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| ***[[3tmg]] - BbABC proline transporter – ''Borrelia burgdorferi''<br / >
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| **Polar amino acid ABC transporter
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| ***[[3hv1]] - ABC polar amino acids transporter SBD – ''Streptococcus thermophilus''<br />
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| **Unspecified amino acid ABC transporter
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| ***[[3c41]] - GsABC amino acids transporter +AMP-PNP <br />
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| ***[[3c4j]] - GsABC amino acids transporter +ATPgS<br />
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| ***[[2olj]] - EcABC amino acid transporter+ADP/Mg – ''Escherichia coli''<br />
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| ***[[2olk]] - EcABC amino acid transporter+ADP-beta-S<br />
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| ***[[2ouk]] - EcABC amino acid transporter+sulfate<br />
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| ***[[3o6p]] - EfABC amino acids transporter<br />
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| ***[[3ip9]] – AtABC amino acid transporter+GABA<br />
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| **Cationic amino acid ABC transporter
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| ***[[2m8c]] - EcABC amino acids transporter<br />
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| **Oligopeptide ABC transporter
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| ***[[3i5o]], [[1vr5]] - TmABC oligopeptides transporter <br />
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| ***[[4gl8]] - BbABC oligopeptide transporter + peptide<br />
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| ***[[4ikv]], [[4ikw]] - GkABC oligopeptides transporter – ''Geobacillus kaustophilus''<br />
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| ***[[4ikx]], [[4iky]] - GkABC oligopeptides transporter (mutant)<br />
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| ***[[4ikz]] - GkABC oligopeptides transporter (mutant) + alafosfalin<br />
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| ***[[2d5w]] - TtABC oligopeptide transporter + peptide<br />
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| ***[[4gf8]], [[4gfr]] - VcABC oligopeptide transporter – ''Vibrio cholera''<br />
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| * ABC sugar transporters
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| **[[2vk2]] - EcABC galactofuranose transporter +galactofuranose<br />
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| **[[2w7y]] - SpABC sugar transporter+A-trisaccaride – ''Streptococcus pneumoniae''<br />
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| **[[2i58]] - SpABC sugar transporter+raffinose<br />
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| **[[2hq0]], [[2heu]], [[2hfb]] - SpABC sugar transporter<br />
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| **[[3g1w]] - BhABC sugar transporter – ''Bacillus halodurans''<br />
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| **[[2z8d]] - BlABC lacto-N-biose transporter SBD+lacto-N-biose – ''Bifidobacterium longum''<br />
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| **[[2z8e]] - BlABC lacto-N-biose transporter SBD+galacto-N-biose<br />
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| **[[2z8f]] - BlABC lacto-N-biose transporter SBD+lacto-N-tetraose<br />
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| **[[3c6q]] - TmABC sugar transporter (mutant)+beta-xylopyranose<br />
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| **[[2yyz]], [[2qvc]], [[2h3h]], [[2hpg]], [[2ghb]] - TmABC sugar transporter<br />
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| **[[2fn9]] - TmABC sugar transporter (mutant)<br />
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| **[[2o7i]] - TmABC sugar transporter+cellobiose<br />
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| **[[2gha]], [[2fnc]] - TmABC sugar transporter+maltotriose<br />
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| **[[2fn8]] - TmABC sugar transporter+ribose<br />
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| **[[4qse]] - AfABC sugar transporter – ''Agrobacterium fabrum''<br />
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| **[[4qrz]] - AfABC sugar transporter+maltotriose <br />
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| **[[4qsc]] - AfABC sugar transporter+maltose <br />
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| **[[4qsd]] - AfABC sugar transporter+sucrose <br />
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| **[[1vci]], [[1v43]] - PhABC sugar transporter – ''Pyrococcus horikoshii''<br />
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| **[[1oxx]], [[1oxs]], [[1oxt]], [[1oxu]], [[1oxv]] - ABC glucose transporter (mutant) – ''Sulfolobus solfataricus''<br />
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| **[[3l49]] - RsABC ribose transporter – ''Rhodobacter sphaeroides''<br />
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| **[[4joq]] - RsABC ribose transporter (mutant) <br />
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| **[[3rot]] - ABC sugar transporter – ''Legionella pneumophila''<br />
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| **[[4kvf]] - ABC rhamnose transporter – ''Kribbella flavida''<br />
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| **[[4rxt]] - ABC sugar transporter+ arabinose – ''Agrobacterium radiobacter''<br />
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| *ABC maltose transporter see [[Maltose-binding protein]]
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| * ABC metal transporters
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| ** ABC metal transporters
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| ***[[3hh8]] - ABC metal transporter – ''Streptococcus pyogenes''<br />
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| ** ABC cobalt transporters
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| ***[[3gfo]] - ABC cobalt transporter – ''Clostridium perfringens''<br />
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| ** ABC nickel transporters
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| ***[[3t66]] - BhABC nickel transporter (mutant)<br />
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| ***[[4ino]] - HpABC nickel transporter (mutant) – ''Helicobacter pylori''<br />
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| ***[[4ls3]] - HpABC nickel transporter + Ni<br />
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| ***[[4inp]] - HpABC nickel transporter (mutant) + Ni<br />
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| ** ABC tungsten transporters
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| ***[[3lr1]] - ABC tungstate transporter – ''Geobacter sulfurreducens''<br />
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| ***[[2onk]] - AfABC molybdate/tungstate transporter+Mo/W binding protein – ''Archaeoglobus fulgidus''<br />
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| ***[[2onr]] - AfABC molybdate/tungstate transporter+Mo<br />
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| ***[[2ons]] - AfABC molybdate/tungstate transporter+W<br />
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| ***[[4rxl]] - VcABC molybdate transporter + W<br />
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| ** ABC iron transporters
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| ***[[3lhs]], [[3li2]] - SaABC OpuAC ferrichrome transporter fragment+Staphyloferrin A <br />
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| ***[[3mwf]], [[3mwg]] - SaABC siderophore transporter +Staphyloferrin B<br />
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| ***[[3g9q]], [[3hxp]] - BsABC ferrichrome transporter<br />
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| ***[[3be5]], [[3be6]] - EcABC iron transporter <br />
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| ***[[2etv]] - TmABC iron transporter <br />
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| ***[[4h59]], [[4hmo]], [[4hmp]], [[4jcc]] - SpABC iron transporter <br />
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| ***[[4hmq]] - SpABC iron transporter + ferrichrome<br />
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| ** ABC molybden transporters
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| ***[[3d31]] - MaABC sulfate/molybdate transporter – ''Methanosarcina acetivorans''<br />
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| ***[[3cfx]] - MaABC sulfate/molybdate transporter + WO4<br />
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| ***[[3cfz]] - MjABC sulfate/molybdate transporter + WO4<br />
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| ***[[3cg1]] - ABC sulfate/molybdate transporter + WO4 – ''Pyrococcus furiosus''<br />
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| ***[[3cg3]] - PhABC sulfate/molybdate transporter + WO4<br />
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| ** ABC zinc transporters
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| ***[[2ogw]] - EcABC zinc transporter<br />
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| ***[[2xh8]] - SeABC zinc transporter (mutant) – ''Salmonella enterica''<br />
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| ***[[2xqv]] - SeABC zinc transporter + Zn<br />
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| ***[[2xy4]] - SeABC zinc transporter<br />
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| ***[[2ov3]], [[2ov1]], [[1pq4]] - SsABC zinc transporter – ''Synechocystis''<br />
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| * ABC multidrug transporters
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| **[[2onj]] - SaABC multidrug transporter+AMP-PNP<br />
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| **[[2hyd]] - SaABC multidrug transporter<br />
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| **[[1mv5]] - LlABC multidrug transporter ATP binding domain
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| * ABC choline transporters
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| **[[3hcq]] - SmABC choline transporter (mutant) – ''Sinorhizobium meliloti''<br />
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| **[[2rin]] - SmABC choline transporter (mutant)+acetylcholine<br />
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| **[[2reg]] - SmABC choline transporter (mutant)+choline<br />
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| **[[2rej]], [[2rf1]] - SmABC choline transporter (mutant)<br />
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| **[[3o66]] – SaABC choline transporter
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| * ABC alpha-hemolysin transporters
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| **[[2pmk]] - EcABC alpha-hemolysin transporter+TNP-ADP<br />
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| **[[2ff7]] - EcABC alpha-hemolysin transporter+ADP<br />
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| **[[2ffa]], [[2ffb]] - EcABC alpha-hemolysin transporter (mutant)+ADP<br />
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| **[[2fgj]], [[2fgk]], [[2xef]] - EcABC alpha-hemolysin transporter (mutant)+ATP<br />
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| **[[3b5j]] - EcABC alpha-hemolysin transporter (mutant)+TNP-ADP<br />
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| * ABC various compounds transporters
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| **[[2v84]] - ABC spermidine/putrescine transporter – ''Treponema pallidum''<br />
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| **[[4eqb]] - SpABC spermidine/putrescine transporter <br />
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| **[[2qi9]] - EcABC vitamin B12 transporter+BtuD+BtuF<br />
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| **[[1l7v]] - EcABC vitamin B12 transporter+BtuD<br />
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| **[[3p7i]], [[3qk6]], [[3quj]], [[3s4u]] – EcABC alkylphosphonate transporter PHND + aminoethyl phosphonic acid<br />
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| **[[1twy]] - VcABC phosphate transporter <br />
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| **[[4n13]] - BbABC phosphate transporter (mutant)<br />
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| **[[3l6g]], [[3l6h]] – LlABC OpuAC betaine transporter SBD <br />
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| **[[2zzv]] - TtABC solute transporter+lactate+Ca<br />
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| **[[2zzw]] - TtABC solute transporter+lactate+Zn<br />
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| **[[2zzx]] - TtABC solute transporter+lactate<br />
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| **[[3gfv]] - BsABC petrobactin transporter – ''Bacillus subtilis''<br />
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| **[[3bk7]] – ABC ATP-binding – ''Pyrococcus abyssi''<br />
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| **[[3ppn]] - BsABC multiple solute transporter<br />
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| **[[3ppo]], [[3ppp]], [[3ppq]], [[3ppr]] - BsABC multiple solute transporter + solute<br />
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| **[[3hn0]] – ABC NO3 transporter – ''Parabacteroides distasonis''<br />
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| **[[3rlb]] - LlABC vitamin B1 transporter + thiamin<br />
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| **[[4dve]] - LlABC biotin transporter + biotin<br />
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| **[[3uif]] – ABC sulfonate transporter – ''Methylobacillus flagellates''<br />
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| **[[4mfi]] – ABC glycerol phosphate transporter – ''Mycobacterium tuberculosis''<br />
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| *hABC transporters subfamilies
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| **[[3nh6]] – hABCB6 NBD<br />
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| **[[3nhb]] – hABCB6 NBD+ADP<br />
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| **[[3nh9]] – hABCB6 NBD+ATP<br />
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| **[[3nha]] – hABCB6 NBD+ATP+Mg
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| * ABC unspecified transporters
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| **[[3lvu]] - SpABC transporter SBD <br />
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| **[[2ihy]] - SaABC transporter ATPase subunit <br />
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| **[[4k3v]] - SaABC transporter<br />
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| **[[3eaf]] - ABC transporter SBD – ''Aeropyrum pernix''<br />
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| **[[3c9h]] - AtABC transporter – ''Agrobacterium tumefaciens''<br />
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| **[[1vpl]], [[1ji0]] - TmABC transporter <br />
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| **[[2pcj]], [[2pcl]] - ABC transporter – ''Aquifex aeolicus''<br />
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| **[[3rpw]] - ABC transporter – ''Rhodopseudomonas palustris''<br />
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| **[[2yl4]], [[3zdq]], [[4ayt]], [[4ayw]], [[4ayx]] - hABC transporter B 10<br />
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| **[[4g68]] – ABC transporter - ''Caldanaerobius''<br />
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| **[[4wwh]] – ABC transporter + galactose – ''Mycobacterium smegmatis''<br />
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| * Cystic fibrosis transmembrane conductance regulator (CFTR)
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| **[[3gd7]] – hCFTR/malK+N6-phenylethyl-ATP<br />
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| **[[2pze]], [[2pzf]], [[2pzg]] – hCFTR NBD1<br />
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| **[[2bbo]], [[2bbs]], [[2bbt]] - hCFTR NBD1 (mutant)<br />
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| **[[1xmi]], [[2xmj]], [[1xmj]] - hCFTR NBD1 (mutant)+ATP<br />
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| **[[1xf9]], [[2xfa]], [[1xfa]] - mCFTR NBD1 (mutant) - mouse<br />
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| **[[1q3h]] - mCFTR NBD1+AMPPNP<br />
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| **[[1r0w]] - mCFTR NBD1<br />
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| **[[1r0x]], [[1r0z]], [[1r10]] - mCFTR NBD1+ATP<br />
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| **[[1r0y]] - mCFTR NBD1+ADP<br />
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| **[[1ckw]], [[1ckx]], [[1cky]], [[1ckz]] – CFTR F508 region - NMR
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| }}
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| == References == | | == References == |
| {{reflist| | | {{reflist| |
