21fo
CYMAL-7-bound 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] Publication Abstract from PubMedMultidrug resistance in Pseudomonas aeruginosa is strongly promoted by the resistance-nodulation-division (RND) family tripartite efflux pump MexAB-OprM, whose inner-membrane transporter MexB plays a central role in recognizing and extruding a broad spectrum of antibiotics and detergents. Although crystal structures of MexB have been determined, no structure of MexB bound to an antibiotic has previously been reported. Here, we report crystal structures of drug-free MexB and chloramphenicol-bound MexB crystallized under mildly basic conditions. In the chloramphenicol-bound structure, chloramphenicol binds at the deep end of the distal binding pocket (DBP) groove in the Binding protomer. Based on this structure, we identified DBP residues (Q125, R128, F178, G179, S180, and Q273) that contact chloramphenicol and evaluated their contributions using in vitro chloramphenicol resistance assays of single-substitution MexB variants. Substitutions at these positions reduced cell growth in the presence of chloramphenicol, minocycline, levofloxacin, and the detergent CYMAL-7. These findings identify a MexB-specific recognition subsite within the DBP groove and provide a structural basis for understanding how MexB recognizes chloramphenicol and other chemically diverse substrates. Structure of chloramphenicol-bound MexB reveals residues in the distal binding pocket that are critical for substrate recognition.,Ueda Y, Yonehara R, Ishizaka-Ikeda E, Nakagawa A, Yamashita E J Biochem. 2026 Feb 9:mvag012. doi: 10.1093/jb/mvag012. PMID:41662826[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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