3S0Z

Crystal structure of New Delhi Metallo-beta-lactamase (NDM-1)

3S0Z の概要

• エントリーDOI: 10.2210/pdb3s0z/pdb
• 分子名称: Metallo-beta-lactamase, ZINC ION (3 entities in total)
• 機能のキーワード: new delhi metallo-beta-lactamase 1, ndm-1, drug resistant, drug discovery, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47430.77

構造登録者

Guo, Y.,Wang, J.,Niu, G.J.,Shui, W.Q.,Sun, Y.N.,Lou, Z.Y.,Rao, Z.H. (登録日: 2011-05-13, 公開日: 2011-06-01, 最終更新日: 2023-11-01)

主引用文献

Guo, Y.,Wang, J.,Niu, G.,Shui, W.,Sun, Y.,Zhou, H.,Zhang, Y.,Yang, C.,Lou, Z.,Rao, Z.
A structural view of the antibiotic degradation enzyme NDM-1 from a superbug.
Protein Cell, 2011

PubMed Abstract: Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibioticresistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.

PubMed: 21637961
DOI: 10.1007/s13238-011-1055-9

実験手法

X-RAY DIFFRACTION (2.5 Å)