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2v4d
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 2v4d is ON HOLD Authors: Symmons, M.F., Bokma, E., Koronakis, E., Hughes, C., Koronakis, V. Description: Re-refinement of MexA adaptor protein ''P...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Re-refinement of MexA adaptor protein== | |
| + | <StructureSection load='2v4d' size='340' side='right'caption='[[2v4d]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2v4d]] is a 13 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V4D FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2v4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4d OCA], [https://pdbe.org/2v4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v4d RCSB], [https://www.ebi.ac.uk/pdbsum/2v4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v4d ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MEXA_PSEAE MEXA_PSEAE] The periplasmic linker component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the pump increases antibiotic and solvent efflux capacities. Required for assembly of the MexA/MexB/OprM complex. Implicated in the secretion of the siderophore pyoverdine.<ref>PMID:8226684</ref> <ref>PMID:8540696</ref> <ref>PMID:9603892</ref> The ability to export antibiotics and solvents is dramatically decreased in the presence of the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), showing that an energized inner membrane is required for efflux. It is thought that the MexB subunit is a proton antiporter.<ref>PMID:8226684</ref> <ref>PMID:8540696</ref> <ref>PMID:9603892</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v4/2v4d_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=2v4d ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bacteria like Escherichia coli and Pseudomonas aeruginosa expel drugs via tripartite multidrug efflux pumps spanning both inner and outer membranes and the intervening periplasm. In these pumps a periplasmic adaptor protein connects a substrate-binding inner membrane transporter to an outer membrane-anchored TolC-type exit duct. High-resolution structures of all 3 components are available, but a pump model has been precluded by the incomplete adaptor structure, because of the apparent disorder of its N and C termini. We reveal that the adaptor termini assemble a beta-roll structure forming the final domain adjacent to the inner membrane. The completed structure enabled in vivo cross-linking to map intermolecular contacts between the adaptor AcrA and the transporter AcrB, defining a periplasmic interface between several transporter subdomains and the contiguous beta-roll, beta-barrel, and lipoyl domains of the adaptor. With short and long cross-links expressed as distance restraints, the flexible linear topology of the adaptor allowed a multidomain docking approach to model the transporter-adaptor complex, revealing that the adaptor docks to a transporter region of comparative stability distinct from those key to the proposed rotatory pump mechanism, putative drug-binding pockets, and the binding site of inhibitory DARPins. Finally, we combined this docking with our previous resolution of the AcrA hairpin-TolC interaction to develop a model of the assembled tripartite complex, satisfying all of the experimentally-derived distance constraints. This AcrA(3)-AcrB(3)-TolC(3) model presents a 610,000-Da, 270-A-long efflux pump crossing the entire bacterial cell envelope. | ||
| - | + | The assembled structure of a complete tripartite bacterial multidrug efflux pump.,Symmons MF, Bokma E, Koronakis E, Hughes C, Koronakis V Proc Natl Acad Sci U S A. 2009 Apr 2. PMID:19342493<ref>PMID:19342493</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2v4d" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Pseudomonas aeruginosa]] | ||
| + | [[Category: Bokma E]] | ||
| + | [[Category: Hughes C]] | ||
| + | [[Category: Koronakis E]] | ||
| + | [[Category: Koronakis V]] | ||
| + | [[Category: Symmons MF]] | ||
Current revision
Re-refinement of MexA adaptor protein
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