title: Structural basis for imipenem inhibition of class C beta-lactamases.
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.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, Illinois 60611-3008, USA.
authors.forename: Beth M
authors.initials: BM
authors.lastname: Beadle
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D018360:Crystallography, X-Ray; D015378:Imipenem / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D065093:beta-Lactamase Inhibitors; D015378:Imipenem; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1