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

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

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 bot...

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Veröffentlicht in:Organic & biomolecular chemistry 2006-01, Vol.4 (2), p.206-210
Hauptverfasser: Hermann, Johannes C, Ridder, Lars, Höltje, Hans-Dieter, Mulholland, Adrian J
Format: Artikel
Sprache:eng
Schlagworte:
Acylation
Anti-Bacterial Agents - metabolism
beta-Lactamases - metabolism
Drug Resistance, Bacterial
Escherichia coli Proteins
Models, Chemical
Penicillin G - metabolism
Quantum Theory
Water - chemistry
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Zusammenfassung: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.
ISSN:1477-0520
1477-0539
DOI:10.1039/b512969a