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

✍ Scribed by Dustin King; Natalie Strynadka

• Publisher: Cold Spring Harbor Laboratory Press
• Year: 2011
• Tongue: English
• Weight: 291 KB
• Volume: 20
• Category: Article
• ISSN: 0961-8368
• DOI: 10.1002/pro.697

✦ Synopsis

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.