DFT studies on reaction mechanism of arsenite oxidase

Abstract

Arsenite oxidase, a Mo/Fe enzyme is involved in detoxification of arsenic (As) from AsIII to less toxic AsV. Density functional theory (DFT) studies have been performed on the active site model geometries of arsenite oxidase generated from X-ray crystal structure data of Alcaligenes feacalis with PDB ID: 1G8J. To study the active site configuration and its effect on the reaction mechanism of arsenite oxidase, two model complex geometries of active site were generated; Active Site Configuration-A and Active Site Configuration-B. In both active site configurations the Mo-center is coordinated with four sulfur atoms of two antiparallel molybdopterin guanosine dinucleotide (MGD) cofactor and a hydroxo (OH) group or oxygen (OW) at 5th coordination site. All the model complex geometries were optimized at B3LYP/SDD(P)//B3LYP/LANL2DZ(P) level of DFT method for transfer of electrons from arsenite to Mo present at active site of arsenite oxidase. Computational results show that model Active Site Configuration-A has an unfavorable geometry for the transfer of electrons from AsIII to Mo-center with conversion of arsenite [H2AsO3]- to arsenate [H2AsO4]-as it has energy barrier of -38.9 kcal/mol whereas Active Site Configuration-B follow the potential energy surface (PES) path and shows a favorable geometry with energy barrier of 18.8 kcal/mol.