title: Crystal structure of New Delhi metallo-β-lactamase reveals molecular basis for antibiotic resistance.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Blood Research, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Dustin
authors.initials: D
authors.lastname: King
authors.forename: Natalie
authors.initials: N
authors.lastname: Strynadka
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods*; D004352:Drug Resistance, Microbial / Q000235:genetics / Q000502:physiology; D007711:Klebsiella pneumoniae / Q000201:enzymology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1