Molecular mechanisms of antibiotic resistance: QM/MM modelling of deacylation in a class A beta-lactamase.

Johannes C Hermann, Lars Ridder, Hans-Dieter Höltje, Adrian J Mulholland

Journal: Organic & biomolecular chemistry 2007;4(2):206-10

PMID: 16391762

Full Text on Royal Society of Chemistry View on PubMed

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.

Address: School of Chemistry, University of Bristol, Bristol, BS8 1TS, U.K.

DOI: 10.1039/b512969a

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Full Text Sources:

https://doi.org/10.1039/b512969a

MeSH Terms: Acylation, Anti-Bacterial Agents, Drug Resistance, Bacterial, Escherichia coli Proteins, Models, Chemical, Penicillin G, Quantum Theory, Water, beta-Lactamases