Catalytic Mechanism for 2,3-Dihydroxybiphenyl Ring-Cleavage by Non-Heme Extradiol Dioxygenases Bphc: Insights from QM/MM Analysis

An extradiol-cleaving catecholic dioxygenase, BphC, plays important roles in catabolism of biphenyl/polychlorinated biphenyls (PCBs) aromatic contaminants in the environment. To better elucidate the biodegradable pathway, a theoretical investigation of the ring-open degradation for 2,3-dihydroxybiphenyl (DHBP) was performed with the aid of quantum mechanical/molecular mechanical (QM/MM) calculations. A quintet state of the DHBP-iron-dioxygen group adducts was found to be reactive ground state with a substrate radical-FeII-superoxo (DHBP• ↑-FeII-O2• ‾↓) character. The HOO• species was the reactive oxygen species responsible for subsequent attack of DHBP. Among the whole reaction energy profile, the first step proton-coupled electron transfer was determined to be the rate-determining step with a potential energy barrier of 17.2 kcal/mol, which is close to the experimental value (14.7 kcal/mol). Importantly, the residue His194 shows distinct roles in the catalytic cycle, where it acts as an acid-base catalys...