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| ==Crystal structure of the drug-discharge outer membrane protein, OprM== | | ==Crystal structure of the drug-discharge outer membrane protein, OprM== |
| <StructureSection load='1wp1' size='340' side='right' caption='[[1wp1]], [[Resolution|resolution]] 2.56Å' scene=''> | | <StructureSection load='1wp1' size='340' side='right'caption='[[1wp1]], [[Resolution|resolution]] 2.56Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1wp1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WP1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WP1 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1wp1]] is a 2 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=1WP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WP1 FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">oprM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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]] 2.56Å</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=1wp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wp1 OCA], [http://pdbe.org/1wp1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wp1 RCSB], [http://www.ebi.ac.uk/pdbsum/1wp1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wp1 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=1wp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wp1 OCA], [https://pdbe.org/1wp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wp1 RCSB], [https://www.ebi.ac.uk/pdbsum/1wp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wp1 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/OPRM_PSEAE OPRM_PSEAE]] The outer membrane 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. Can replace the OprJ outer membrane component of the MexCD-OprJ pump; the antibiotics exported are those exported by the intact MexCD pump, showing that efflux substrate specificity is not conferred by this component. Serves as the outer membrane component for the MexXY efflux system. Implicated in the secretion of the siderophore pyoverdine. OprM is probably involved in the efflux of the siderophore across the outer membrane.<ref>PMID:8226684</ref> <ref>PMID:8540696</ref> <ref>PMID:9401051</ref> <ref>PMID:9603892</ref> <ref>PMID:10952562</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:9401051</ref> <ref>PMID:9603892</ref> <ref>PMID:10952562</ref> | | [https://www.uniprot.org/uniprot/OPRM_PSEAE OPRM_PSEAE] The outer membrane 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. Can replace the OprJ outer membrane component of the MexCD-OprJ pump; the antibiotics exported are those exported by the intact MexCD pump, showing that efflux substrate specificity is not conferred by this component. Serves as the outer membrane component for the MexXY efflux system. Implicated in the secretion of the siderophore pyoverdine. OprM is probably involved in the efflux of the siderophore across the outer membrane.<ref>PMID:8226684</ref> <ref>PMID:8540696</ref> <ref>PMID:9401051</ref> <ref>PMID:9603892</ref> <ref>PMID:10952562</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:9401051</ref> <ref>PMID:9603892</ref> <ref>PMID:10952562</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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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=1wp1 ConSurf]. | | </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=1wp1 ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The OprM lipoprotein of Pseudomonas aeruginosa is a member of the MexAB-OprM xenobiotic-antibiotic transporter subunits that is assumed to serve as the drug discharge duct across the outer membrane. The channel structure must differ from that of the porin-type open pore because the protein facilitates the exit of antibiotics but not the entry. For better understanding of the structure-function linkage of this important pump subunit, we studied the x-ray crystallographic structure of OprM at the 2.56-angstroms resolution. The overall structure exhibited trimeric assembly of the OprM monomer that consisted mainly of two domains: the membrane-anchoring beta-barrel and the cavity-forming alpha-barrel. OprM anchors the outer membrane by two modes of membrane insertions. One is via the covalently attached NH(2)-terminal fatty acids and the other is the beta-barrel structure consensus on the outer membrane-spanning proteins. The beta-barrel had a pore opening with a diameter of about 6-8 angstroms, which is not large enough to accommodate the exit of any antibiotics. The periplasmic alpha-barrel was about 100 angstroms long formed mainly by a bundle of alpha-helices that formed a solvent-filled cavity of about 25,000 angstroms(3). The proximal end of the cavity was tightly sealed, thereby not permitting the entry of any molecule. The result of this structure was that the resting state of OprM had a small outer membrane pore and a tightly closed periplasmic end, which sounds plausible because the protein should not allow free access of antibiotics. However, these observations raised another unsolved problem about the mechanism of opening of the OprM cavity ends. The crystal structure offers possible mechanisms of pore opening and pump assembly.
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| Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa: dual modes of membrane anchoring and occluded cavity end.,Akama H, Kanemaki M, Yoshimura M, Tsukihara T, Kashiwagi T, Yoneyama H, Narita S, Nakagawa A, Nakae T J Biol Chem. 2004 Dec 17;279(51):52816-9. Epub 2004 Oct 26. PMID:15507433<ref>PMID:15507433</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1wp1" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Porin|Porin]] | | *[[Porin 3D structures|Porin 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Akama, H]] | | [[Category: Large Structures]] |
| [[Category: Kanemaki, M]] | | [[Category: Pseudomonas aeruginosa]] |
| [[Category: Kashiwagi, T]] | | [[Category: Akama H]] |
| [[Category: Nakae, T]] | | [[Category: Kanemaki M]] |
| [[Category: Nakagawa, A]] | | [[Category: Kashiwagi T]] |
| [[Category: Narita, S]] | | [[Category: Nakae T]] |
| [[Category: Tsukihara, T]] | | [[Category: Nakagawa A]] |
| [[Category: Yoshimura, M]] | | [[Category: Narita S]] |
| [[Category: Beta barrel]]
| | [[Category: Tsukihara T]] |
| [[Category: Membrane protein]]
| | [[Category: Yoshimura M]] |