Chloroperoxidase (CPO) is a highly versatile enzyme capable of catalyzing a broad spectrum of oxidation reactions, including enantiospecific epoxidation and sulfoxidation, halogenation, dehalogenation, N-methylation, and dismutation. For this reason, CPO is the subject of research aimed at bioengineering an industrial chiral biocatalyst.  Our simulation work focuses on the structure-function relationship of CPO and the cause of the enzyme's high enantioselectivity. We describe MD simulations revealing that breathing of the active pocket, including reorientation of the catalytic Glu, modulates CPO between P450-like and peroxidase-like reactivity.  Biased-MD simulations exposing sources of epoxidation enantioselectivity and NMR/simulated annealing revealing the source of unexpected oxidation reactivity toward indole are also presented. Our most recent QM work on small, active-site models reveals that hydrogen bonding to the proximal sulfur both reduces the barrier for formation of Compound 0 from the peroxide-bound ferric species, and modulates the mechanism of formation of Compound 1 from Compound 0. Additionally, we present evidence that the electric dipole created by the proximal helix may be partially responsible for some enantioselectivity.

Reactivity of chloroperoxidase, a promising bioengineering target, revealed through simulation

247th National Meeting (2014)

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