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New mechanistic insights into coupled binuclear copper monooxygenases from the recent elucidation of the ternary intermediate of tyrosinase
Author(s) -
Kipouros Ioannis,
Solomon Edward I.
Publication year - 2023
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14503
Subject(s) - tyrosinase , chemistry , hydroxylation , monooxygenase , stereochemistry , copper protein , catechol oxidase , biocatalysis , ternary operation , aryl , protonation , ternary complex , bioinorganic chemistry , enzyme , combinatorial chemistry , copper , catalysis , reaction mechanism , organic chemistry , alkyl , cytochrome p450 , peroxidase , ion , polyphenol oxidase , computer science , programming language
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 μ‐η 2 :η 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 μ‐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.