Computational Study of Catalytic Reaction of Quercetin 2,4-Dioxygenase

We present a quantum mechanics/molecular mechanics (QM/MM) and QM only study on the oxidative ring cleaving reaction of quercetin catalyzed by quercetin 4-dioxygenase (2,4-QD). 2,4-QD has,a mononuclear type 2 copper center and incorporates two oxygen atoms at C2 and C4 positions of the substrate. It has not been clear Whether dioxygen reacts with a copper ion Or a substrate radical as the first step. We have Sound that dioxygen is more likely to bind to a Cu2+ ion, involving-the dissociation of the substrate from the copper ion. Then a Cu2+-alkylperox complex can be generated., Comparison of geometry and stability between QM-only and QM/MM results Strongly indicates that steric effects of the protein environment contribute to maintain the Orientation of the substrate dissociated from the copper center. The present QM/MM results also highlight. that prior rearrangement of the Cu2+-alkylperoxo complex and a subsequent hydrogen bond switching assisted by the Movement of Glu73 can facilitate formation of an endoperoxide intermediate Selectively.