5XP9

Crystal structure of Bismuth bound NDM-1

5XP9 の概要

• エントリーDOI: 10.2210/pdb5xp9/pdb
• 分子名称: Metallo-beta-lactamase type 2, Bismuth(III) ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: antibiotics resistance, beta-lactamase, metallodrug, bismuth, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• 細胞内の位置: Periplasm : C7C422
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26019.97

構造登録者

Zhang, H.,Ma, G.,Lai, T.P.,Sun, H. (登録日: 2017-06-01, 公開日: 2018-03-07, 最終更新日: 2023-11-22)

主引用文献

Wang, R.,Lai, T.P.,Gao, P.,Zhang, H.,Ho, P.L.,Woo, P.C.,Ma, G.,Kao, R.Y.,Li, H.,Sun, H.
Bismuth antimicrobial drugs serve as broad-spectrum metallo-beta-lactamase inhibitors
Nat Commun, 9:439-439, 2018

PubMed Abstract: Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.

PubMed: 29382822
DOI: 10.1038/s41467-018-02828-6

実験手法

X-RAY DIFFRACTION (1.55 Å)