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Copper–Oxygen Dynamics in the Tyrosinase Mechanism
Author(s) -
Fujieda Nobutaka,
Umakoshi Kyohei,
Ochi Yuta,
Nishikawa Yosuke,
Yanagisawa Sachiko,
Kubo Minoru,
Kurisu Genji,
Itoh Shinobu
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202004733
Subject(s) - tyrosinase , chemistry , peroxide , substrate (aquarium) , catalysis , copper , active site , ligand (biochemistry) , phenols , photochemistry , oxygen , reaction mechanism , stereochemistry , enzyme , organic chemistry , receptor , biochemistry , oceanography , geology
The dinuclear copper enzyme, tyrosinase, activates O 2 to form a (μ‐η 2 :η 2 ‐p eroxido)dicopper(II) species, which hydroxylates phenols to catechols. However, the exact mechanism of phenolase reaction in the catalytic site of tyrosinase is still under debate. We herein report the near atomic resolution X‐ray crystal structures of the active tyrosinases with substrate l ‐tyrosine. At their catalytic sites, CuA moved toward l ‐tyrosine (CuA1 → CuA2), whose phenol oxygen directly coordinates to CuA2, involving the movement of CuB (CuB1 → CuB2). The crystal structures and spectroscopic analyses of the dioxygen‐bound tyrosinases demonstrated that the peroxide ligand rotated, spontaneously weakening its O−O bond. Thus, the copper migration induced by the substrate‐binding is accompanied by rearrangement of the bound peroxide species so as to provide one of the peroxide oxygen atoms with access to the phenol substrate's ϵ carbon atom.