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Antimicrobial Agents and Chemotherapy, December 2002, p. 3978-3980, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3978-3980.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Structural Basis for Imipenem Inhibition of Class C ß-Lactamases

Beth M. Beadle and Brian K. Shoichet*

Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, Illinois 60611-3008

Received 1 May 2002/ Returned for modification 25 June 2002/ Accepted 23 August 2002

To determine how imipenem inhibits the class C ß-lactamase AmpC, the X-ray crystal structure of the acyl-enzyme complex was determined to a resolution of 1.80 Å. In the complex, the lactam carbonyl oxygen of imipenem has flipped by approximately 180° 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.

* Corresponding author. Mailing address: Department of Molecular Pharmacology & Biological Chemistry, Northwestern University, 303 E. Chicago Ave. S215, Chicago, IL 60611-3008. Phone (312) 503-0081. Fax (312) 503-5349. E-mail: b-shoichet{at}northwestern.edu.

Antimicrobial Agents and Chemotherapy, December 2002, p. 3978-3980, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3978-3980.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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