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Protein Sci. 2011 Sep;20(9):1484-91. doi: 10.1002/pro.697. Epub 2011 Aug 2.

Crystal structure of New Delhi metallo-β-lactamase reveals molecular basis for antibiotic resistance.

Author information

1
Department of Biochemistry and Molecular Biology and Center for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

β-Lactams are the most commonly prescribed class of antibiotics and have had an enormous impact on human health. Thus, it is disquieting that an enzyme called New Delhi metallo-β-lactamase-1 (NDM-1) can confer Enterobacteriaceae with nearly complete resistance to all β-lactam antibiotics including the carbapenams. We have determined the crystal structure of Klebsiella pneumoniae apo-NDM-1 to 2.1-Å resolution. From the structure, we see that NDM-1 has an expansive active site with a unique electrostatic profile, which we propose leads to a broader substrate specificity. In addition, NDM-1 undergoes important conformational changes upon substrate binding. These changes have not been previously observed in metallo-β-lactamase enzymes and may have a direct influence on substrate recognition and catalysis.

PMID:
21774017
PMCID:
PMC3190144
DOI:
10.1002/pro.697
[Indexed for MEDLINE]
Free PMC Article

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