Structural basis for the interaction of lactivicins with serine beta-lactamases.
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.
Brown
Tom
T
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.
Charlier
Paulette
P
Herman
Raphaël
R
Schofield
Christopher J
CJ
Sauvage
Eric
E
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
D000900:Anti-Bacterial Agents; D010455:Peptides; D010456:Peptides, Cyclic; C051231:lactivicin; D012694:Serine; D001618:beta-Lactamases