21FP

Chloramphenicol-bound MexB

21FP の概要

• エントリーDOI: 10.2210/pdb21fp/pdb
• 分子名称: Multidrug resistance protein MexB, CHLORAMPHENICOL (2 entities in total)
• 機能のキーワード: drug efflux, rnd transporter, membrane protein
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 342167.95

構造登録者

Ueda, Y.,Yonehara, R.,Nakagawa, A.,Yamashita, E. (登録日: 2025-12-11, 公開日: 2026-05-06, 最終更新日: 2026-06-03)

主引用文献

Ueda, Y.,Yonehara, R.,Ishizaka-Ikeda, E.,Nakagawa, A.,Yamashita, E.
Structure of chloramphenicol-bound MexB reveals residues in the distal binding pocket that are critical for substrate recognition.
J.Biochem., 179:403-411, 2026

PubMed Abstract: Multidrug 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.

PubMed: 41662826
DOI: 10.1093/jb/mvag012

実験手法

X-RAY DIFFRACTION (2.89 Å)