6JKB

Crystal structure of metallo-beta-lactamse, NDM-1, in complex with hydrolyzed ampicillin

6JKB の概要

• エントリーDOI: 10.2210/pdb6jkb/pdb
• 分子名称: Metallo-beta-lactamase type 2, ZINC ION, (2R,4S)-2-[(R)-{[(2R)-2-amino-2-phenylacetyl]amino}(carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: hydrolase, antibiotic
• 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: 52568.45

構造登録者

Kamo, T.,Kuroda, K.,Kondo, S.,Hayashi, U.,Fudo, S.,Nukaga, M.,Hoshino, T. (登録日: 2019-02-28, 公開日: 2020-03-25, 最終更新日: 2023-11-22)

主引用文献

Kamo, T.,Kuroda, K.,Kondo, S.,Hayashi, U.,Fudo, S.,Yoneda, T.,Takaya, A.,Nukaga, M.,Hoshino, T.
Identification of the Inhibitory Compounds for Metallo-beta-lactamases and Structural Analysis of the Binding Modes.
Chem Pharm Bull (Tokyo), 69:1179-1183, 2021

PubMed Abstract: Metallo-β-lactamases (MBLs) are significant threats to humans because they deteriorate many kinds of β-lactam antibiotics and are key enzymes responsible for multi-drug resistance of bacterial pathogens. As a result of in vitro screening, two compounds were identified as potent inhibitors of two kinds of MBLs: imipenemase (IMP-1) and New Delhi metallo-β-lactamase (NDM-1). The binding structure of one of the identified compounds was clarified by an X-ray crystal analysis in complex with IMP-1, in which two possible binding poses were observed. Molecular dynamics (MD) simulations were performed by building two calculation models from the respective binding poses. The compound was stably bound to the catalytic site during the simulation in one pose. The binding model between NDM-1 and the compound was constructed for MD simulation. Calculation results for NDM-1 were similar to those of IMP-1. The simulation suggested that the binding of the identified inhibitory compound was also durable in the catalytic site of NDM-1. The compound will be a sound basis for the development of the inhibitors for MBLs.

PubMed: 34853284
DOI: 10.1248/cpb.c21-00611

実験手法

X-RAY DIFFRACTION (2.444 Å)