title: Binding of (5S)-penicilloic acid to penicillin binding protein 3.
abstract: β-Lactam antibiotics react with penicillin binding proteins (PBPs) to form relatively stable acyl-enzyme complexes. We describe structures derived from the reaction of piperacillin with PBP3 (Pseudomonas aeruginosa) including not only the anticipated acyl-enzyme complex but also an unprecedented complex with (5S)-penicilloic acid, which was formed by C-5 epimerization of the nascent (5R)-penicilloic acid product. Formation of the complex was confirmed by solution studies, including NMR. Together, these results will be useful in the design of new PBP inhibitors and raise the possibility that noncovalent PBP inhibition by penicilloic acids may be of clinical relevance.
authors.affiliation: Chemistry Research Laboratory, University of Oxford , 12 Mansfield Road, Oxford OX1 3TA, U.K.
authors.forename: Sander S
authors.initials: SS
authors.lastname: van Berkel
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Nettleship
authors.forename: Ivanhoe K H
authors.initials: IK
authors.lastname: Leung
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brem
authors.forename: Hwanho
authors.initials: H
authors.lastname: Choi
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
authors.forename: Timothy D W
authors.initials: TD
authors.lastname: Claridge
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDonough
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Owens
authors.forename: Jingshan
authors.initials: J
authors.lastname: Ren
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D046915:Penicillin-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D011549:Pseudomonas / Q000201:enzymology
chemical_list: D056831:Coordination Complexes; D046915:Penicillin-Binding Proteins; C008782:penicilloic acid; D010397:Penicillanic Acid