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| | <StructureSection load='6iia' size='340' side='right'caption='[[6iia]], [[Resolution|resolution]] 2.91Å' scene=''> | | <StructureSection load='6iia' size='340' side='right'caption='[[6iia]], [[Resolution|resolution]] 2.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6iia]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IIA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IIA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6iia]] is a 6 chain structure with sequence from [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=6IIA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IIA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AV0:2-decyl-2-{[(4-O-alpha-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]methyl}dodecyl+4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside'>AV0</scene></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]] 2.91Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3w9i|3w9i]], [[3w9j|3w9j]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AV0:2-decyl-2-{[(4-O-alpha-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]methyl}dodecyl+4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside'>AV0</scene></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=6iia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iia OCA], [http://pdbe.org/6iia PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iia RCSB], [http://www.ebi.ac.uk/pdbsum/6iia PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iia 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=6iia FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iia OCA], [https://pdbe.org/6iia PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iia RCSB], [https://www.ebi.ac.uk/pdbsum/6iia PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iia ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MEXB_PSEAE MEXB_PSEAE]] The inner membrane transporter 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. 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> | + | [https://www.uniprot.org/uniprot/MEXB_PSEAE MEXB_PSEAE] The inner membrane transporter 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. 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 == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nakao, K]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Nakashima, R]] | + | [[Category: Nakao K]] |
| - | [[Category: Sakurai, K]]
| + | [[Category: Nakashima R]] |
| - | [[Category: Membrane protein]] | + | [[Category: Sakurai K]] |
| - | [[Category: Multidrug]] | + | |
| - | [[Category: Transporter]]
| + | |
| Structural highlights
Function
MEXB_PSEAE The inner membrane transporter 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. 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
RND-type multidrug efflux pumps have two voluminous multisite drug-binding pockets named the proximal and distal binding pocket. High- and low-molecular-mass drugs bind to these proximal and distal pocket, respectively. Here, we report the crystal structures of MexB of Pseudomonas aeruginosa bound with high-molecular-mass compounds. Contrary to the expectations, lauryl maltose neopentyl glycol (LMNG, MW 1,005), which is a surfactant larger than the proximal pocket-binding drugs, was found to bind to the distal pocket: one of the two hydrophobic alkyl chains was inserted into the hydrophobic pit, which is the binding site of the efflux pump inhibitor ABI-PP. LMNG is a substrate of the MexAB-OprM system and competitively inhibits the export of other substrates by this system. However, LMNG does not inhibit the export of other substrates by the inhibitor-binding-pit mutant F178W, which retains the export activity of LMNG. The crystal structure of this mutant suggested that the alkyl chain of LMNG could no longer be inserted into the pit because of steric hindrance. We also determined the crystal structure of MexB containing the high-molecular-mass compound neopentyl glycol derivative C7NG (MW 1,028), the binding site of which overlapped with LMNG in the distal pocket, indicating that whether a substrate binds to the distal or proximal pockets is controlled not only by its molecular weight but also by its individual molecular characteristic.
Crystal structures of multidrug efflux pump MexB bound with high-molecular-mass compounds.,Sakurai K, Yamasaki S, Nakao K, Nishino K, Yamaguchi A, Nakashima R Sci Rep. 2019 Mar 13;9(1):4359. doi: 10.1038/s41598-019-40232-2. PMID:30867446[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
- ↑ Sakurai K, Yamasaki S, Nakao K, Nishino K, Yamaguchi A, Nakashima R. Crystal structures of multidrug efflux pump MexB bound with high-molecular-mass compounds. Sci Rep. 2019 Mar 13;9(1):4359. doi: 10.1038/s41598-019-40232-2. PMID:30867446 doi:http://dx.doi.org/10.1038/s41598-019-40232-2
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