The reaction mechanism of hydroxyethylphosphonate dioxygenase: a QM/MM study

Abstract

By employing ab initio quantum mechanical/molecular mechanical (QM/MM) and molecular dynamics (MD) simulations, we have provided further evidence against the previously proposed hydroperoxylation or hydroxylation mechanism of hydroxyethylphosphonate dioxygenase (HEPD). HEPD employs an interesting catalytic cycle based on concatenated bifurcations. The first bifurcation is based on the abstraction of hydrogen atoms from the substrate, which leads to a distal or proximal hydroperoxo species (Fe–OOH or Fe–(OH)O). The second and the third bifurcations refer to the carbon–carbon bond cleavage reaction. And this is achieved through a tridentate intermediate, or employing a proton-shuttle assisted mechanism, in which the residue Glu₁₇₆ or the Fe^IVO group serves as a general base. The reaction directions seem to be tunable and show significant environment dependence. This mechanism can provide a comprehensive interpretation for the seemingly contradicting experimental evidences and provide insight into the development of biochemistry and material sciences.