1t9y

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[[Image:1t9y.gif|left|200px]]
 
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==Structural Basis of Multidrug Transport by the AcrB Multidrug Efflux Pump==
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The line below this paragraph, containing "STRUCTURE_1t9y", creates the "Structure Box" on the page.
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<StructureSection load='1t9y' size='340' side='right'caption='[[1t9y]], [[Resolution|resolution]] 3.64&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1t9y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T9Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T9Y FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.64&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MC2:N2-(L-PHENYLALANYL)-N1-(NAPHTHALENYL)-L-ARIGNINAMIDE'>MC2</scene></td></tr>
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{{STRUCTURE_1t9y| PDB=1t9y | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t9y OCA], [https://pdbe.org/1t9y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t9y RCSB], [https://www.ebi.ac.uk/pdbsum/1t9y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t9y ProSAT]</span></td></tr>
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</table>
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'''Structural Basis of Multidrug Transport by the AcrB Multidrug Efflux Pump'''
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== Function ==
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[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>
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== Evolutionary Conservation ==
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==Overview==
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[[Image:Consurf_key_small.gif|200px|right]]
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The Escherichia coli AcrB multidrug efflux pump is a membrane protein that recognizes many structurally dissimilar toxic compounds. We previously reported the X-ray structures of four AcrB-ligand complexes in which the ligands were bound to the wall of the extremely large central cavity in the transmembrane domain of the pump. Genetic studies, however, suggested that discrimination between the substrates occurs mainly in the periplasmic domain rather than the transmembrane domain of the pump. We here describe the crystal structures of the AcrB mutant in which Asn109 was replaced by Ala, with five structurally diverse ligands, ethidium, rhodamine 6G, ciprofloxacin, nafcillin, and Phe-Arg-beta-naphthylamide. The ligands bind not only to the wall of central cavity but also to a new periplasmic site within the deep external depression formed by the C-terminal periplasmic loop. This depression also includes residues identified earlier as being important in the specificity. We show here that conversion into alanine of the Phe664, Phe666, or Glu673 residue in the periplasmic binding site produced significant decreases in the MIC of most agents in the N109A background. Furthermore, decreased MICs were also observed when these residues were mutated in the wild-type AcrB background, although the effects were more modest. The MIC data were also confirmed by assays of ethidium influx rates in intact cells, and our results suggest that the periplasmic binding site plays a role in the physiological process of drug efflux.
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Check<jmol>
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<jmolCheckbox>
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==About this Structure==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t9/1t9y_consurf.spt"</scriptWhenChecked>
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1T9Y is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T9Y OCA].
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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==Reference==
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</jmolCheckbox>
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A periplasmic drug-binding site of the AcrB multidrug efflux pump: a crystallographic and site-directed mutagenesis study., Yu EW, Aires JR, McDermott G, Nikaido H, J Bacteriol. 2005 Oct;187(19):6804-15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16166543 16166543]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1t9y ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: McDermott, G.]]
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[[Category: McDermott G]]
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[[Category: Nikaido, H.]]
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[[Category: Nikaido H]]
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[[Category: Yu, E W.]]
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[[Category: Yu EW]]
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[[Category: 12 transmembrane]]
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[[Category: Membrane protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:43:29 2008''
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Current revision

Structural Basis of Multidrug Transport by the AcrB Multidrug Efflux Pump

PDB ID 1t9y

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