6iol
Cryo-EM structure of multidrug efflux pump MexAB-OprM (60 degree state)
Structural highlights
FunctionMEXA_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 PubMedIn Pseudomonas aeruginosa, MexAB-OprM plays a central role in multidrug resistance by ejecting various drug compounds, which is one of the causes of serious nosocomial infections. Although the structures of the components of MexAB-OprM have been solved individually by X-ray crystallography, no structural information for fully assembled pumps from P. aeruginosa were previously available. In this study, we present the structure of wild-type MexAB-OprM in the presence or absence of drugs at near-atomic resolution. The structure reveals that OprM does not interact with MexB directly, and that it opens its periplasmic gate by forming a complex. Furthermore, we confirm the residues essential for complex formation and observed a movement of the drug entrance gate. Based on these results, we propose mechanisms for complex formation and drug efflux. Structures of the wild-type MexAB-OprM tripartite pump reveal its complex formation and drug efflux mechanism.,Tsutsumi K, Yonehara R, Ishizaka-Ikeda E, Miyazaki N, Maeda S, Iwasaki K, Nakagawa A, Yamashita E Nat Commun. 2019 Apr 3;10(1):1520. doi: 10.1038/s41467-019-09463-9. PMID:30944318[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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