Enantioselectivity of haloalkane dehalogenase LinB on the degradation of 1,2-dichloropropane: A QM/MM study

Abstract

The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8kcal/mol for the (R)-isomer and 24.0kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP.