title: Structural basis for the interaction of lactivicins with serine beta-lactamases.
abstract: Lactivicin (LTV) is a natural non-beta-lactam antibiotic that inhibits penicillin-binding proteins and serine beta-lactamases. A crystal structure of a BS3-LTV complex reveals that, as for its reaction with PBPs, LTV reacts with the nucleophilic serine and that cycloserine and lactone rings of LTV are opened. This structure, together with reported structures of PBP1b with lactivicins, provides a basis for developing improved lactivicin-based gamma-lactam antibiotics.
authors.affiliation: Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Brown
authors.forename: Paulette
authors.initials: P
authors.lastname: Charlier
authors.forename: Raphaël
authors.initials: R
authors.lastname: Herman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.forename: Eric
authors.initials: E
authors.lastname: Sauvage
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001407:Bacillus / Q000201:enzymology; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic; D012694:Serine / Q000378:metabolism*; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D010456:Peptides, Cyclic; C051231:lactivicin; D012694:Serine; D001618:beta-Lactamases