Structural basis for imipenem inhibition of class C beta-lactamases

Antimicrob Agents Chemother. 2002 Dec;46(12):3978-80. doi: 10.1128/aac.46.12.3978-3980.2002.

Abstract

To determine how imipenem inhibits the class C beta-lactamase AmpC, the X-ray crystal structure of the acyl-enzyme complex was determined to a resolution of 1.80 A. In the complex, the lactam carbonyl oxygen of imipenem has flipped by approximately 180 degrees compared to its expected position; the electrophilic acyl center is thus displaced from the point of hydrolytic attack. This conformation resembles that of imipenem bound to the class A enzyme TEM-1 but is different from that of moxalactam bound to AmpC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins*
  • Crystallography, X-Ray
  • Imipenem / pharmacology*
  • Structure-Activity Relationship
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / drug effects*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamase Inhibitors
  • Imipenem
  • AmpC beta-lactamases
  • beta-Lactamases
  • beta-lactamase TEM-1