title: Role of ser-237 in the substrate specificity of the carbapenem-hydrolyzing class A beta-lactamase Sme-1.
abstract: The role of the serine residue found at position 237 in the carbapenemase Sme-1 has been investigated by constructing a mutant in which Ser-237 was replaced by an alanine. The S237A mutant showed a catalytic behavior against penicillins and aztreonam very similar to that of Sme-1. By contrast, S237A was characterized by a reduced catalytic efficiency against cephems, such as cephalothin and cephaloridine. In addition, the weak activity of Sme-1 against the cephamycin cefoxitin was hardly detectable with the mutant enzyme. Finally, the Ser-237-->Ala mutation resulted in a marked decrease in catalytic activity against imipenem, showing that Ser-237 contributes to the carbapenemase activity of the class A beta-lactamase Sme-1.
authors.affiliation: Laboratoire de Recherche Moléculaire sur les Antibiotiques (LRMA), Faculté de Médecine Pitié-Salpêtrière, Université Pierre et Marie Curie, 91 boulevard de l'Hôpital, F-75634, Paris Cedex 13, Paris, France. sougakof@lmcp.jussieu.fr
authors.forename: W
authors.initials: W
authors.lastname: Sougakoff
authors.forename: T
authors.initials: T
authors.lastname: Naas
authors.forename: P
authors.initials: P
authors.lastname: Nordmann
authors.forename: E
authors.initials: E
authors.lastname: Collatz
authors.forename: V
authors.initials: V
authors.lastname: Jarlier
mesh_terms: D000409:Alanine / Q000737:chemistry; D015780:Carbapenems / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis; D015378:Imipenem / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D012694:Serine / Q000737:chemistry*; D013379:Substrate Specificity; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D015780:Carbapenems; D012694:Serine; D015378:Imipenem; C094219:beta-lactamase Sme-1; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D000409:Alanine