|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of MacA-MexA chimeric protein, containing the Pseudomonas aeruginosa MexA alpha-hairpin domain.== | | ==Crystal Structure of MacA-MexA chimeric protein, containing the Pseudomonas aeruginosa MexA alpha-hairpin domain.== |
| - | <StructureSection load='4dk1' size='340' side='right' caption='[[4dk1]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='4dk1' size='340' side='right'caption='[[4dk1]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dk1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_acetinomycetum_comitans"_(sic)_(klinger_1912)_colebrook_1920 "bacterium acetinomycetum comitans" (sic) (klinger 1912) colebrook 1920]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DK1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DK1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dk1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aggregatibacter_actinomycetemcomitans Aggregatibacter actinomycetemcomitans] and [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DK1 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dk0|4dk0]]</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=4dk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dk1 OCA], [https://pdbe.org/4dk1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dk1 RCSB], [https://www.ebi.ac.uk/pdbsum/4dk1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dk1 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mexA, PA0425 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=714 "Bacterium acetinomycetum comitans" (sic) (Klinger 1912) Colebrook 1920])</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=4dk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dk1 OCA], [http://pdbe.org/4dk1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dk1 RCSB], [http://www.ebi.ac.uk/pdbsum/4dk1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dk1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [[https://www.uniprot.org/uniprot/Q2EHL9_AGGAC Q2EHL9_AGGAC]] [[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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ha, N C]] | + | [[Category: Aggregatibacter actinomycetemcomitans]] |
| - | [[Category: Xu, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Alpha-hairpin]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Beta-barrel domain]] | + | [[Category: Ha NC]] |
| - | [[Category: Lipoyl]] | + | [[Category: Xu Y]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Periplasmic protein]]
| + | |
| Structural highlights
Function
[Q2EHL9_AGGAC] [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.[1] [2] [3] 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.[4] [5] [6]
Publication Abstract from PubMed
Gram-negative bacteria are capable of expelling diverse xenobiotic substances from within the cell by use of three-component efflux pumps in which the energy-activated inner membrane transporter is connected to the outer membrane channel protein via the membrane fusion protein. In this work, we describe the crystal structure of the membrane fusion protein MexA from the Pseudomonas aeruginosa MexAB-OprM pump in the hexameric ring arrangement. Electron microscopy study on the chimeric complex of MexA and the outer membrane protein OprM reveals that MexA makes a tip-to-tip interaction with OprM, which suggests a docking model for MexA and OprM. This docking model agrees well with genetic results and depicts detailed interactions. Opening of the OprM channel is accompanied by the simultaneous exposure of a protein structure resembling a six-bladed cogwheel, which intermeshes with the complementary cogwheel structure in the MexA hexamer. Taken together, we suggest an assembly and channel opening model for the MexAB-OprM pump. This study provides a better understanding of multidrug resistance in Gram-negative bacteria.
Assembly and channel opening of outer membrane protein in tripartite drug efflux pumps of Gram-negative bacteria.,Xu Y, Moeller A, Jun SY, Le M, Yoon BY, Kim JS, Lee K, Ha NC J Biol Chem. 2012 Apr 6;287(15):11740-50. Epub 2012 Feb 3. PMID:22308040[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol. 1993 Nov;175(22):7363-72. PMID:8226684
- ↑ Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1948-53. PMID:8540696
- ↑ Li XZ, Zhang L, Poole K. Role of the multidrug efflux systems of Pseudomonas aeruginosa in organic solvent tolerance. J Bacteriol. 1998 Jun;180(11):2987-91. PMID:9603892
- ↑ Xu Y, Moeller A, Jun SY, Le M, Yoon BY, Kim JS, Lee K, Ha NC. Assembly and channel opening of outer membrane protein in tripartite drug efflux pumps of Gram-negative bacteria. J Biol Chem. 2012 Apr 6;287(15):11740-50. Epub 2012 Feb 3. PMID:22308040 doi:http://dx.doi.org/10.1074/jbc.M111.329375
|
