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| | ==Conformation of the AcrB Multidrug Efflux Pump in Mutants of the Putative Proton Relay Pathway== | | ==Conformation of the AcrB Multidrug Efflux Pump in Mutants of the Putative Proton Relay Pathway== |
| - | <StructureSection load='2hqd' size='340' side='right' caption='[[2hqd]], [[Resolution|resolution]] 3.65Å' scene=''> | + | <StructureSection load='2hqd' size='340' side='right'caption='[[2hqd]], [[Resolution|resolution]] 3.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2hqd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HQD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HQD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2hqd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HQD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HQD FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1t9t|1t9t]], [[2hqc|2hqc]], [[2hqf|2hqf]], [[2hqg|2hqg]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.65Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acrB, acrE, b0462 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=2hqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hqd OCA], [https://pdbe.org/2hqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hqd RCSB], [https://www.ebi.ac.uk/pdbsum/2hqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hqd ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hqd OCA], [http://pdbe.org/2hqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hqd RCSB], [http://www.ebi.ac.uk/pdbsum/2hqd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hqd 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> | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hq/2hqd_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hq/2hqd_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Gu, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, M]] | + | [[Category: Gu R]] |
| - | [[Category: McDermott, G]] | + | [[Category: Li M]] |
| - | [[Category: Nikaido, H]] | + | [[Category: McDermott G]] |
| - | [[Category: Su, C C]] | + | [[Category: Nikaido H]] |
| - | [[Category: Takatsuka, Y]] | + | [[Category: Su C-C]] |
| - | [[Category: Yu, E W]] | + | [[Category: Takatsuka Y]] |
| - | [[Category: Membrane protein]]
| + | [[Category: Yu EW]] |
| - | [[Category: Multidrug efflux pump]]
| + | |
| Structural highlights
Function
ACRB_ECOLI AcrAB is a drug efflux protein with a broad substrate specificity.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We previously reported the X-ray structures of wild-type Escherichia coli AcrB, a proton motive force-dependent multidrug efflux pump, and its N109A mutant. These structures presumably reflect the resting state of AcrB, which can bind drugs. After ligand binding, a proton may bind to an acidic residue(s) in the transmembrane domain, i.e., Asp407 or Asp408, within the putative network of electrostatically interacting residues, which also include Lys940 and Thr978, and this may initiate a series of conformational changes that result in drug expulsion. Herein we report the X-ray structures of four AcrB mutants, the D407A, D408A, K940A, and T978A mutants, in which the structure of this tight electrostatic network is expected to become disrupted. These mutant proteins revealed remarkably similar conformations, which show striking differences from the previously known conformations of the wild-type protein. For example, the loop containing Phe386 and Phe388, which play a major role in the initial binding of substrates in the central cavity, becomes prominently extended into the center of the cavity, such that binding of large substrate molecules may become difficult. We believe that this new conformation may mimic, at least partially, one of the transient conformations of the transporter during the transport cycle.
Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway.,Su CC, Li M, Gu R, Takatsuka Y, McDermott G, Nikaido H, Yu EW J Bacteriol. 2006 Oct;188(20):7290-6. PMID:17015668[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murakami S, Nakashima R, Yamashita E, Matsumoto T, Yamaguchi A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature. 2006 Sep 14;443(7108):173-9. Epub 2006 Aug 16. PMID:16915237 doi:10.1038/nature05076
- ↑ Seeger MA, Schiefner A, Eicher T, Verrey F, Diederichs K, Pos KM. Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism. Science. 2006 Sep 1;313(5791):1295-8. PMID:16946072 doi:313/5791/1295
- ↑ Sennhauser G, Amstutz P, Briand C, Storchenegger O, Grutter MG. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol. 2007 Jan;5(1):e7. PMID:17194213 doi:10.1371/journal.pbio.0050007
- ↑ Su CC, Li M, Gu R, Takatsuka Y, McDermott G, Nikaido H, Yu EW. Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway. J Bacteriol. 2006 Oct;188(20):7290-6. PMID:17015668 doi:http://dx.doi.org/188/20/7290
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