Mechanism of O2 activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases.

ABSTRACT: Peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM) are copper-dependent enzymes that are vital for neurotransmitter regulation and hormone biosynthesis. These enzymes feature a unique active site consisting of two spatially separated (by 11 Å in PHM) and magnetically noncoupled copper centers that enables 1e^- activation of O₂ for hydrogen atom abstraction (HAA) of substrate C-H bonds and subsequent hydroxylation. Although the structures of the resting enzymes are known, details of the hydroxylation mechanism and timing of long-range electron transfer (ET) are not clear. This study presents density-functional calculations of the full reaction coordinate, which demonstrate: (i) the importance of the end-on coordination of superoxide t

SUBMITTER: Cowley RE 

PROVIDER: S-EPMC5087064 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature