A Molecular Modeling Study of the Catalytic Mechanism of Haloalkane Dehalogenase:  1. Quantum Chemical Study of the First Reaction Step

The haloalkane dehalogenase of soil bacteria Xanthobacter autotrophicus is an enzyme, which catalyzes the environmentally important detoxification process, namelythe hydrolytic cleavage of the carbon−halogen bond. A molecular modeling study has been conducted with the structures of the wild-type enzyme and its mutants in order to investigate the mechanisms of the dehalogenation reaction at molecular level. Semiempirical quantum chemical calculations have been applied to elucidate the importance of the active site residues for kinetic and thermodynamic characteristics in the first step of dehalogenation reaction. The results obtained from these calculations have been compared with previously published experimental results. The strength of the application of molecular modeling method for the study of the evolutionary aspects of biodegradation of organic pollutants is discussed.