title: Crystal structure of the Mycobacterium fortuitum class A beta-lactamase: structural basis for broad substrate specificity.
abstract: beta-Lactamases are the main cause of bacterial resistance to penicillins and cephalosporins. Class A beta-lactamases, the largest group of beta-lactamases, have been found in many bacterial strains, including mycobacteria, for which no beta-lactamase structure has been previously reported. The crystal structure of the class A beta-lactamase from Mycobacterium fortuitum (MFO) has been solved at 2.13-A resolution. The enzyme is a chromosomally encoded broad-spectrum beta-lactamase with low specific activity on cefotaxime. Specific features of the active site of the class A beta-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 beta-lactamases but lacks a specific feature of these enzymes, the VNYN motif (residues 103 to 106), which confers on CTX-M-type extended-spectrum beta-lactamases a more efficient cefotaximase activity.
authors.affiliation: Centre d'Ingénierie des Protéines, Université de Liège, Institut de Physique B5, B-4000 Liège, Belgium. eric.sauvage@ulg.ac.be
authors.forename: Eric
authors.initials: E
authors.lastname: Sauvage
authors.forename: Eveline
authors.initials: E
authors.lastname: Fonzé
authors.forename: Birgit
authors.initials: B
authors.lastname: Quinting
authors.forename: Moreno
authors.initials: M
authors.lastname: Galleni
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Frère
authors.forename: Paulette
authors.initials: P
authors.lastname: Charlier
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001665:Binding Sites; D002439:Cefotaxime / Q000378:metabolism; D003460:Crystallization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019907:Mycobacterium fortuitum / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases; D002439:Cefotaxime