Abstract

Flavoenzymes catalyze C-H bond cleavage via a hydride transfer mechanism and single electron transfer in numerous cellular reactions. Flavoenzymes are also capable of activating molecular oxygen to catalyze hydroxylation, epoxidation, and Baeyer-Villiger reactions. These oxygenation reactions require formation of a C4a-(hydro)peroxyflavin (FlOO(H)) intermediate. In certain cases, this covalent intermediate is very stable, with reported half-lives of several minutes. Covalent intermediates have also been shown to occur in non-redox reactions where the reduced flavin is required for activity, such as in the isomerization of UDP-galactopyranose to UDP-galactofuranose by UDP-galactopyranose mutase (UGM) and in the dehalogenation reaction catalyzed by 2-haloacrylate hydratase (2HAH). Our mechanistic, structural, and computational data describing the mechanism of stabilization of the FlOO(H), with a focus on the role of NADP+, will be presented. Results of our studies on the UGM and 2HAH reactions will highlight the multiple functionalities of flavins, which include acting as covalent catalysts, nucleophile, radical chemistry, stabilization of protein conformations, and as a proton shuttle. Support or Funding Information The research reported here was supported by grants from the National Institute of General Medical Sciences (NIGMS) award R01GM094469 and the National Science Foundation award CHE-1506206. The major reactive centers of flavin cofactors This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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