5LCH

VIM-2 metallo-beta-lactamase in complex with (S)-1-allyl-2-(3-methoxyphenyl)-3-oxoisoindoline-4-carboxylic acid (compound 42)

5LCH の概要

• エントリーDOI: 10.2210/pdb5lch/pdb
• 分子名称: Metallo-beta-lactamase VIM-2, ZINC ION, (1~{S})-2-(3-methoxyphenyl)-3-oxidanylidene-1-prop-2-enyl-1~{H}-isoindole-4-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: metallo-beta-lactamase, inhibitor, complex, antibiotic resistance, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28807.00

構造登録者

Li, G.-B.,Brem, J.,McDonough, M.A.,Schofield, C.J. (登録日: 2016-06-21, 公開日: 2017-02-15, 最終更新日: 2024-01-10)

主引用文献

Li, G.B.,Abboud, M.I.,Brem, J.,Someya, H.,Lohans, C.T.,Yang, S.Y.,Spencer, J.,Wareham, D.W.,McDonough, M.A.,Schofield, C.J.
NMR-filtered virtual screening leads to non-metal chelating metallo-beta-lactamase inhibitors.
Chem Sci, 8:928-937, 2017

PubMed Abstract: There are no clinically useful inhibitors of metallo-β-lactamases (MBLs), which are a growing problem because they hydrolyse almost all β-lactam antibacterials. Inhibition by most reported MBL inhibitors involves zinc ion chelation. A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of the clinically relevant Verona Integron-encoded MBL (VIM)-2. Crystallographic analyses reveal a new mode of MBL inhibition involving binding adjacent to the active site zinc ions, but which does not involve metal chelation. The results will aid efforts to develop new types of clinically useful inhibitors targeting MBLs/MBL-fold metallo-enzymes involved in antibacterial and anticancer drug resistance.

PubMed: 28451231
DOI: 10.1039/c6sc04524c

実験手法

X-RAY DIFFRACTION (1.94 Å)