title: Molecular mechanisms of antibiotic resistance: QM/MM modelling of deacylation in a class A beta-lactamase.
abstract: Modelling of the first step of the deacylation reaction of benzylpenicillin in the E. coli TEM1 beta-lactamase (with B3LYP/6-31G + (d)//AM1-CHARMM22 quantum mechanics/molecular mechanics methods) shows that a mechanism in which Glu166 acts as the base to deprotonate a conserved water molecule is both energetically and structurally consistent with experimental data; the results may assist the design of new antibiotics and beta-lactamase inhibitors.
authors.affiliation: School of Chemistry, University of Bristol, Bristol, BS8 1TS, U.K.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Hermann
authors.forename: Lars
authors.initials: L
authors.lastname: Ridder
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Höltje
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
mesh_terms: D000215:Acylation; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D029968:Escherichia coli Proteins; D008956:Models, Chemical; D010400:Penicillin G / Q000378:metabolism; D011789:Quantum Theory; D014867:Water / Q000737:chemistry; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D014867:Water; D001618:beta-Lactamases; D010400:Penicillin G