Effect of electrostatic interaction on the mechanism of dehalogenation catalyzed by haloalkane dehalogenase

Theoretical calculation has been carried out for the nucleophilic displacement reaction of 1,2-dichloroethane catalyzed by haloalkane dehalogenase. The results indicate that different hydrogen bond patterns of the oxyanion hole and the halide-stabilizing residues play an important role in the dehalogenation reaction. They cause concertedly an earlier transition state (TS) with the activation barrier of 16.60 kcal/mol. The stabilization effect of Trp125 and Trp175 on chlorine atom in the TS is larger than that of the reactant complex by 15.67 kcal/mol so that, they make contribution to the stabilization of the TS. Moreover, the reaction shows the enzymatic action can be attributed to a combination of reactant-state destabilization and transition-state electrostatic stabilization. (C) 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011