Hybrid QM/MM and DFT investigations of the catalytic mechanism and inhibition of the dinuclear zinc metallo-beta-lactamase CcrA from Bacteroides fragilis

The mechanistic and energetic features of the catalytic action of dizinc metallo-beta-lactamase CcrA from Bacteroides fragilis is investigated based on hybrid QM/MM molecular dynamics simulation and density functional theoretical (DFT) calculations. The high catalytic activity of the CcrA enzyme stems from a simultaneous operation of three catalytic components, which includes activation of the bridging hydroxide nucleophile by zinc-coordinated Asp86.