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

Modelling of the first step of the deacylation reaction of benzylpenicllin in the E. coli TEM1 P-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 P-lactamase inhibitors.