Molecular dynamics simulations of the mononuclear zinc-beta-lactamase fromBacillus cereus

Herein, we report molecular dynamics simulations of the mononuclear form of the Bacillus cereus zinc-P-lactamase. We studied two different configurati ons which differ in the presence of a zinc-bound hydroxide or a zinc-bound water and in the protonation state of the essential His210 residue. Contact s of the catalytically important residues (Asp90, His210, Cys168, etc.) wit h the zinc center are characterized by the MD analyses. The nature of the Z n-OH2 --> His210 proton transfer pathway connecting the two configurations was studied by means of QM calculations on cluster models while the relativ e stability of the two configurations was estimated from QM/MM calculations in the enzyme. From these results, a theoretical model for the kinetically active form of the B. cer-eus metalloenzyme is proposed. Some mechanistic implications and the influence of mutating the Cys168 residue are also disc ussed.