4RL0

Structural and mechanistic insights into NDM-1 catalyzed hydrolysis of cephalosporins

4RL0 の概要

• エントリーDOI: 10.2210/pdb4rl0/pdb
• 分子名称: Beta-lactamase NDM-1, ZINC ION, (2R,5S)-5-[(carbamoyloxy)methyl]-2-[(R)-carboxy{[(2Z)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino}methyl]-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: ndm-1 antibiotic hydrolysis, 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: 2
• 化学式量合計: 52410.08

構造登録者

Feng, H.,Ding, J.,Zhu, D.,Liu, X.,Xu, X.,Zhang, Y.,Zang, S.,Wang, D.-C.,Liu, W. (登録日: 2014-10-14, 公開日: 2014-11-19, 最終更新日: 2024-02-28)

主引用文献

Feng, H.,Ding, J.,Zhu, D.,Liu, X.,Xu, X.,Zhang, Y.,Zang, S.,Wang, D.C.,Liu, W.
Structural and Mechanistic Insights into NDM-1 Catalyzed Hydrolysis of Cephalosporins.
J.Am.Chem.Soc., 136:14694-14697, 2014

PubMed Abstract: Cephalosporins constitute a large class of β-lactam antibiotics clinically used as antimicrobial drugs. New Dehli metallo-β-lactamase (NDM-1) poses a global threat to human health as it confers on bacterial pathogen resistance to almost all β-lactams, including penicillins, cephalosporins, and carbapenems. Here we report the first crystal structures of NDM-1 in complex with cefuroxime and cephalexin, as well as NMR spectra monitoring cefuroxime and cefixime hydrolysis catalyzed by NDM-1. Surprisingly, cephalosporoate intermediates were captured in both crystal structures determined at 1.3 and 2.0 Å. These results provide detailed information concerning the mechanism and pathways of cephalosporin hydrolysis. We also present the crystal structure and enzyme assays of a D124N mutant, which reveals that D124 most likely plays a more structural than catalytic role.

PubMed: 25268575
DOI: 10.1021/ja508388e

実験手法

X-RAY DIFFRACTION (1.3 Å)