4C1H

Crystal structure of the metallo-beta-lactamase BCII with L-captopril

4C1H の概要

• エントリーDOI: 10.2210/pdb4c1h/pdb
• 関連するPDBエントリー: 4BZ3 4C09 4C1C 4C1D 4C1E 4C1F 4C1G
• 分子名称: BETA-LACTAMASE 2, GLYCEROL, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, mbl, metallo-beta-lactamase, antibiotic resistance
• 由来する生物種: BACILLUS CEREUS
• 細胞内の位置: Periplasm : P04190
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25623.89

構造登録者

Zollman, D.,Brem, J.,McDonough, M.A.,van Berkel, S.S.,Schofield, C.J. (登録日: 2013-08-12, 公開日: 2014-08-27, 最終更新日: 2023-12-20)

主引用文献

Brem, J.,van Berkel, S.S.,Zollman, D.,Lee, S.Y.,Gileadi, O.,McHugh, P.J.,Walsh, T.R.,McDonough, M.A.,Schofield, C.J.
Structural Basis of Metallo-beta-Lactamase Inhibition by Captopril Stereoisomers.
Antimicrob. Agents Chemother., 60:142-150, 2015

PubMed Abstract: β-Lactams are the most successful antibacterials, but their effectiveness is threatened by resistance, most importantly by production of serine- and metallo-β-lactamases (MBLs). MBLs are of increasing concern because they catalyze the hydrolysis of almost all β-lactam antibiotics, including recent-generation carbapenems. Clinically useful serine-β-lactamase inhibitors have been developed, but such inhibitors are not available for MBLs. l-Captopril, which is used to treat hypertension via angiotensin-converting enzyme inhibition, has been reported to inhibit MBLs by chelating the active site zinc ions via its thiol(ate). We report systematic studies on B1 MBL inhibition by all four captopril stereoisomers. High-resolution crystal structures of three MBLs (IMP-1, BcII, and VIM-2) in complex with either the l- or d-captopril stereoisomer reveal correlations between the binding mode and inhibition potency. The results will be useful in the design of MBL inhibitors with the breadth of selectivity required for clinical application against carbapenem-resistant Enterobacteriaceae and other organisms causing MBL-mediated resistant infections.

PubMed: 26482303
DOI: 10.1128/AAC.01335-15

実験手法

X-RAY DIFFRACTION (1.1 Å)