6LJ5

Crystal structure of NDM-1 in complex with D-captopril derivative wss04145

6LJ5 の概要

• エントリーDOI: 10.2210/pdb6lj5/pdb
• 関連するPDBエントリー: 5ZJ2 6LIP 6LIZ 6LJ0 6LJ1 6LJ2 6LJ4
• 分子名称: Metallo-beta-lactamase type 2, 1,2-ETHANEDIOL, 1-[(2S)-2-methyl-3-sulfanyl-propanoyl]piperidine-4-carboxylic acid, ... (5 entities in total)
• 機能のキーワード: ndm-1, metallo-beta-lactamase, antibiotic resistent, inhibitor, thio compounds, antibiotic, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26056.02

構造登録者

Zhang, H.,Ma, G. (登録日: 2019-12-13, 公開日: 2020-12-16, 最終更新日: 2023-11-22)

主引用文献

Ma, G.,Wang, S.,Wu, K.,Zhang, W.,Ahmad, A.,Hao, Q.,Lei, X.,Zhang, H.
Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.
Bioorg.Med.Chem., 29:115902-115902, 2020

PubMed Abstract: β-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-β-lactamase 1 (NDM-1) is able to hydrolyze nearly all β-lactam antibiotics and even clinically used serine-β-lactamase inhibitors. The wide and rapid spreading of NDM-1 gene among pathogenic bacteria has attracted extensive attention, therefore high potency NDM-1 inhibitors are urgently needed. Here we report a series of structure-guided design of D-captopril derivatives that can inhibit the activity of NDM-1 in vitro and at cellular levels. Structural comparison indicates the mechanisms of inhibition enhancement and provides insights for further inhibitor optimization.

PubMed: 33302045
DOI: 10.1016/j.bmc.2020.115902

実験手法

X-RAY DIFFRACTION (1.26 Å)