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| | <StructureSection load='4c48' size='340' side='right'caption='[[4c48]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='4c48' size='340' side='right'caption='[[4c48]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4c48]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli], [http://en.wikipedia.org/wiki/Ecow3 Ecow3] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C48 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4C48 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4c48]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12], [https://en.wikipedia.org/wiki/Escherichia_coli_str._K-12_substr._W3110 Escherichia coli str. K-12 substr. W3110] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4C48 FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4c48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c48 OCA], [http://pdbe.org/4c48 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4c48 RCSB], [http://www.ebi.ac.uk/pdbsum/4c48 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4c48 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4c48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4c48 OCA], [https://pdbe.org/4c48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4c48 RCSB], [https://www.ebi.ac.uk/pdbsum/4c48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4c48 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACRB_ECOLI ACRB_ECOLI]] AcrAB is a drug efflux protein with a broad substrate specificity.<ref>PMID:16915237</ref> <ref>PMID:16946072</ref> <ref>PMID:17194213</ref> [[http://www.uniprot.org/uniprot/ACRZ_ECOLI ACRZ_ECOLI]] AcrA-AcrB-AcrZ-TolC is a drug efflux protein complex with a broad substrate specificity. This protein binds to AcrB and is required for efflux of some but not all substrates, suggesting it may influence the specificity of drug export.<ref>PMID:23010927</ref> | + | [[https://www.uniprot.org/uniprot/ACRB_ECOLI ACRB_ECOLI]] AcrAB is a drug efflux protein with a broad substrate specificity.<ref>PMID:16915237</ref> <ref>PMID:16946072</ref> <ref>PMID:17194213</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The capacity of numerous bacterial species to tolerate antibiotics and other toxic compounds arises in part from the activity of energy-dependent transporters. In Gram-negative bacteria, many of these transporters form multicomponent 'pumps' that span both inner and outer membranes and are driven energetically by a primary or secondary transporter component. A model system for such a pump is the acridine resistance complex of Escherichia coli. This pump assembly comprises the outer-membrane channel TolC, the secondary transporter AcrB located in the inner membrane, and the periplasmic AcrA, which bridges these two integral membrane proteins. The AcrAB-TolC efflux pump is able to transport vectorially a diverse array of compounds with little chemical similarity, thus conferring resistance to a broad spectrum of antibiotics. Homologous complexes are found in many Gram-negative species, including in animal and plant pathogens. Crystal structures are available for the individual components of the pump and have provided insights into substrate recognition, energy coupling and the transduction of conformational changes associated with the transport process. However, how the subunits are organized in the pump, their stoichiometry and the details of their interactions are not known. Here we present the pseudo-atomic structure of a complete multidrug efflux pump in complex with a modulatory protein partner from E. coli. The model defines the quaternary organization of the pump, identifies key domain interactions, and suggests a cooperative process for channel assembly and opening. These findings illuminate the basis for drug resistance in numerous pathogenic bacterial species.
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| - | Structure of the AcrAB-TolC multidrug efflux pump.,Du D, Wang Z, James NR, Voss JE, Klimont E, Ohene-Agyei T, Venter H, Chiu W, Luisi BF Nature. 2014 Apr 20. doi: 10.1038/nature13205. PMID:24747401<ref>PMID:24747401</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4c48" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Ecow3]] | + | [[Category: Escherichia coli str. K-12 substr. W3110]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Du, D]] | + | [[Category: Du D]] |
| - | [[Category: James, N]] | + | [[Category: James N]] |
| - | [[Category: Klimont, E]] | + | [[Category: Klimont E]] |
| - | [[Category: Luisi, B F]] | + | [[Category: Luisi BF]] |
| - | [[Category: Drug efflux]]
| + | |
| - | [[Category: Transmembrane protein]]
| + | |
| - | [[Category: Transport protein]]
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