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Molecular Dynamics Simulations of the Mononuclear Zinc-β-lactamase from Bacillus Cereus
journal contribution
posted on 2001-03-29, 00:00 authored by Dimas Suárez, Kenneth M. MerzHerein, we report molecular dynamics simulations of the mononuclear form of the Bacillus cereus
zinc-β-lactamase. We studied two different configurations 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. Contacts of the catalytically
important residues (Asp90, His210, Cys168, etc.) with the zinc center are characterized by the MD analyses.
The nature of the Zn−OH2 → His210 proton transfer pathway connecting the two configurations was studied
by means of QM calculations on cluster models while the relative 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. cereus metalloenzyme is proposed. Some mechanistic implications and the influence of
mutating the Cys168 residue are also discussed.