Theoretical study on the hydrolytic step in the biotransformation of β-hexachlorocyclohexane degraded by haloalkane dehalogenase LinB

Abstract

The hydrolytic process of LinB-catalyzed biotransformation of a notorious contaminant β-HCH was investigated in atomistic detail with a combined quantum mechanics/molecular mechanics approach. The Boltzmann-weighted averaging method amended by disproportionate effect analysis was showed to capture the fluctuation of a single molecule enzyme reaction. With the potential barriers of 18.7 and 2.6 kcal/mol, two elementary steps that refer to formation and decomposition of a tetrahedral intermediate are involved in the hydrolytic reaction, respectively. Polarized by Glu132, His272 serves as a proton carrier along the whole hydrolysis reaction. The electrostatic influence analysis highlighted residue Leu248 as a possible mutation target for rational design of LinB in enzyme modification. Further spatial location analysis provided explanation for the opposite effect of Asn38 toward the two elementary steps. Getting insight into the catalytic details and the structure and function of LinB can enrich the knowledge of it and promote its application in bioremediation of chlorinated hydrocarbon pollutants.