3S0Z

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

Summary for 3S0Z

• Entry DOI: 10.2210/pdb3s0z/pdb
• Descriptor: Metallo-beta-lactamase, ZINC ION (3 entities in total)
• Functional Keywords: new delhi metallo-beta-lactamase 1, ndm-1, drug resistant, drug discovery, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 47430.77

Authors

Guo, Y.,Wang, J.,Niu, G.J.,Shui, W.Q.,Sun, Y.N.,Lou, Z.Y.,Rao, Z.H. (deposition date: 2011-05-13, release date: 2011-06-01, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)