Alternative Pathway for the Reaction Catalyzed by DNA Dealkylase AlkB from Ab Initio QM/MM Calculations.

ABSTRACT: AlkB is the title enzyme of a family of DNA dealkylases that catalyze the direct oxidative dealkylation of nucleobases. The conventional mechanism for the dealkylation of N¹-methyl adenine (1-meA) catalyzed by AlkB after the formation of Fe^IV-oxo is comprised by a reorientation of the oxo moiety, hydrogen abstraction, OH rebound from the Fe atom to the methyl adduct, and the dissociation of the resulting methoxide to obtain the repaired adenine base and formaldehyde. An alternative pathway with hydroxide as a ligand bound to the iron atom is proposed and investigated by QM/MM simulations. The results show OH^- has a small impact on the barriers for the hydrogen abstraction and OH rebound steps. The effects of the enzyme and the OH^- ligand on the h

SUBMITTER: Fang D 

PROVIDER: S-EPMC4230374 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature