Mechanism of O ₂ activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases

Abstract

Significance Nature has evolved several strategies for using dioxygen (O 2 ) for chemical oxidations. These enzymatic processes typically use metal cofactors to impart selectivity and minimize production of deleterious reactive oxygen species. In particular, hormone biosynthesis and neurotransmitter regulation are accomplished by copper- and O 2 -dependent enzymes possessing a unique copper active site; however, the mechanism has been debated and the role of the unique active site structure in enabling the chemistry is unclear. To understand this, structural and spectroscopic data are used to computationally model the full reaction mechanism to define the molecular basis for O 2 reactivity and define the role of the active site structure in controlling proper enzymatic function.