Dehydrochlorination mechanism of γ-hexachlorocyclohexane degraded by dehydrochlorinase LinA from Sphingomonas paucimobilis UT26

This study investigated the aerobic degradation mechanism of gamma-HCH to 1,3,4,6-TCDN catabolized by dehydrochlorinase LinA from Sphingomonas paucimobilis UT26. The enzymatic step was studied by a combined quantum mechanics/molecular mechanics (QM/MM) computation and the nonenzymatic step was investigated by the DFT method. There are three elementary steps involved in the degradation process. Two discontinuous dehydrochlorination reactions with the Boltzmann-weighted average potential barriers of 16.2 and 17.3 kcal mol(-1) are connected by a conformational transition with a barrier of 11.1 kcal mol(-1). The electrostatic influence analysis of fourteen key residues surrounding the active site has been carried out. The study reveals that Phe68 facilitates the dehydrochlorination of gamma-HCH, whereas Leu21 and Cys71 suppress it. Future mutation studies for improving the degradation efficiency of LinA can focus on mutating the amino acids of Leu21 and Cys71.