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Antimicrobial Agents and Chemotherapy, July 2006, p. 2516-2521, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.01226-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Crystal Structure of the Mycobacterium fortuitum Class A ß-Lactamase: Structural Basis for Broad Substrate Specificity

Eric Sauvage,* Eveline Fonzé, Birgit Quinting, Moreno Galleni, Jean-Marie Frère, and Paulette Charlier

Centre d'Ingénierie des Protéines, Université de Liège, Institut de Physique B5 and Institut de Chimie B6, Sart Tilman, B-4000 Liège, Belgium

Received 20 September 2005/ Returned for modification 27 November 2005/ Accepted 6 April 2006

ß-Lactamases are the main cause of bacterial resistance to penicillins and cephalosporins. Class A ß-lactamases, the largest group of ß-lactamases, have been found in many bacterial strains, including mycobacteria, for which no ß-lactamase structure has been previously reported. The crystal structure of the class A ß-lactamase from Mycobacterium fortuitum (MFO) has been solved at 2.13-Å resolution. The enzyme is a chromosomally encoded broad-spectrum ß-lactamase with low specific activity on cefotaxime. Specific features of the active site of the class A ß-lactamase from M. fortuitum are consistent with its specificity profile. Arg278 and Ser237 favor cephalosporinase activity and could explain its broad substrate activity. The MFO active site presents similarities with the CTX-M type extended-spectrum ß-lactamases but lacks a specific feature of these enzymes, the VNYN motif (residues 103 to 106), which confers on CTX-M-type extended-spectrum ß-lactamases a more efficient cefotaximase activity.

* Corresponding author. Mailing address: Centre d'Ingénierie des Protéines, Université de Liège, Institut de Physique B5, B-4000 Liège, Belgium. Phone: 32-43-66-36-20. Fax: 32-43-66-33-64. E-mail: eric.sauvage{at}ulg.ac.be.

Antimicrobial Agents and Chemotherapy, July 2006, p. 2516-2521, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.01226-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Walther-Rasmussen, J., Hoiby, N. (2007). Class A carbapenemases. J Antimicrob Chemother 60: 470-482 [Abstract] [Full Text]  


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