6Q30

Crystal structure of NDM-1 beta-lactamase in complex with boronic inhibitor cpd 5

6Q30 の概要

• エントリーDOI: 10.2210/pdb6q30/pdb
• 分子名称: Metallo-beta-lactamase type 2, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: beta-lactamase; bacterial resistance; acyclic boronic inhibitors, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52620.28

構造登録者

Maso, L.,Quotadamo, A.,Bellio, P.,Montanari, M.,Celenza, G.,Venturelli, A.,Costi, M.P.,Tondi, D.,Cendron, L. (登録日: 2018-12-03, 公開日: 2019-04-24, 最終更新日: 2024-01-24)

主引用文献

Cendron, L.,Quotadamo, A.,Maso, L.,Bellio, P.,Montanari, M.,Celenza, G.,Venturelli, A.,Costi, M.P.,Tondi, D.
X-ray Crystallography Deciphers the Activity of Broad-Spectrum Boronic Acid beta-Lactamase Inhibitors.
Acs Med.Chem.Lett., 10:650-655, 2019

PubMed Abstract: Recent decades have witnessed a dramatic increase of multidrug resistant (MDR) bacteria, compromising the efficacy of available antibiotics, and a continual decline in the discovery of novel antibacterials. We recently reported the first library of benzo[b]thiophen-2-ylboronic acid inhibitors sharing broad spectrum activity against β-lactamases (BLs). The ability of these compounds to inhibit structurally and mechanistically different types of β-lactamases has been here structurally investigated. An extensive X-ray crystallographic analysis of boronic acids (BAs) binding to proteins representative of serine BLs (SBLs) and metallo β-lactamases (MBLs) have been conducted to depict the role played by the boronic group in driving molecular recognition, especially in the interaction with MBLs. Our derivatives are the first case of noncyclic boronic acids active against MBLs and represent a productive route toward potent broad-spectrum inhibitors.

PubMed: 30996812
DOI: 10.1021/acsmedchemlett.8b00607

実験手法

X-RAY DIFFRACTION (1.5 Å)