2v4d

From Proteopedia

(Difference between revisions)

Revision as of 01:37, 25 December 2014

RE-REFINEMENT OF MEXA ADAPTOR PROTEIN

Structural highlights

2v4d is a 13 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1vf7, 1t5e
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[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
↑ Symmons MF, Bokma E, Koronakis E, Hughes C, Koronakis V. The assembled structure of a complete tripartite bacterial multidrug efflux pump. Proc Natl Acad Sci U S A. 2009 Apr 2. PMID:19342493

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2v4d"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2v4d]] is a 13 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V4D FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1vf7|1vf7]], [[1t5e|1t5e]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1vf7|1vf7]], [[1t5e|1t5e]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2v4d RCSB], [http://www.ebi.ac.uk/pdbsum/2v4d PDBsum]</span></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=2v4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v4d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2v4d RCSB], [http://www.ebi.ac.uk/pdbsum/2v4d PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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]]
@@ Line 30: / Line 32: @@
 </StructureSection>
 [[Category: Pseudomonas aeruginosa]]
-[[Category: Bokma, E.]]
+[[Category: Bokma, E]]
-[[Category: Hughes, C.]]
+[[Category: Hughes, C]]
-[[Category: Koronakis, E.]]
+[[Category: Koronakis, E]]
-[[Category: Koronakis, V.]]
+[[Category: Koronakis, V]]
-[[Category: Symmons, M F.]]
+[[Category: Symmons, M F]]
 [[Category: Antibiotic efflux pump]]
 [[Category: Antibiotic resistance]]

2v4d

From Proteopedia

Revision as of 01:37, 25 December 2014

RE-REFINEMENT OF MEXA ADAPTOR PROTEIN

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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