Catalytic Mechanisms for Cofactor-Free Oxidase-Catalyzed Reactions: Reaction Pathways of Uricase-Catalyzed Oxidation and Hydration of Uric Acid.

ABSTRACT: First-principles quantum mechanical/molecular mechanical (QM/MM)-free energy calculations have been performed to uncover how uricase catalyzes metabolic reactions of uric acid (UA), demonstrating that the entire reaction process of UA in uricase consists of two stages-oxidation followed by hydration. The oxidation consists of four steps: (1) chemical transformation from 8-hydroxyxythine to an anionic radical via a proton transfer along with an electron transfer, which is different from the previously proposed electron-transfer mechanism that involves a dianion intermediate (UA^2-) during the catalytic reaction process; (2) proton transfer to the O₂^- anion (radical); (3) diradical recombination to form a peroxo intermediate; (4) dissociation of H₂

SUBMITTER: Wei D 

PROVIDER: S-EPMC5589204 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature