2v50
The Missing Part of the Bacterial MexAB-OprM System: Structural determination of the Multidrug Exporter MexB
Structural highlights
FunctionMEXB_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] 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 PubMedWe report here the crystal structure of the Pseudomonas aeruginosa multidrug exporter MexB, an intensively studied member of the resistance-nodulation-cell division family of secondary active transporters, at 3.0 A. MexB forms an asymmetric homotrimer where each subunit adopts a different conformation representing three snapshots of the transport cycle similar to the recently determined structures of its close homologue AcrB from Escherichia coli, so far the sole structurally characterized member of the superfamily. As for AcrB, the conformations of two subunits can be clearly assigned to either the binding step or the extrusion step in the transport process. Unexpectedly, a remarkable conformational shift in the third subunit is observed in MexB, which has potential implications for the assembly of the tripartite MexAB-OprM drug efflux system. Furthermore, an n-dodecyl-d-maltoside molecule was found bound to the internal multidrug-binding cavity, which might indicate that MexB binds and transports detergent molecules as substrates. As the only missing piece of the puzzle in the MexAB-OprM system, the X-ray structure of MexB completes the molecular picture of the major pump mediating intrinsic and acquired multidrug resistance in P. aeruginosa. Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa.,Sennhauser G, Bukowska MA, Briand C, Grutter MG J Mol Biol. 2009 May 29;389(1):134-45. Epub 2009 Apr 8. PMID:19361527[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
