New mechanistic insights into coupled binuclear copper monooxygenases from the recent elucidation of the ternary intermediate of tyrosinase

Tyrosinase is the most predominant member of the coupled binuclear copper (CBC) protein family. The recent trapping and spectroscopic definition of the elusive catalytic ternary intermediate (enzyme/O-2/monophenol) of tyrosinase dictates a monooxygenation mechanism that revises previous proposals and involves cleavage of the mu-eta(2):eta(2)-peroxide dicopper(II) O-O bond to accept the phenolic proton, followed by monophenolate coordination to copper concomitant with aromatic hydroxylation by the non-protonated mu-oxo. Here, we compare and contrast previously proposed and current mechanistic models for monophenol monooxygenation of tyrosinase. Next, we discuss how these recent insights provide new opportunities towards uncovering structure-function relationships in CBC enzymes, as well as understanding fundamental principles for O-2 activation and reactivity by bioinorganic active sites.

Automated summary

Tyrosinase, a member of the CBC protein family, has been studied extensively. Recent research has revealed the structure of a catalytic ternary intermediate and proposed a revised mechanism for monophenol monooxygenation. These findings are significant for understanding structure-function relationships in CBC enzymes and the activation of O-2 in bioinorganic active sites.