Copper–Oxygen Dynamics in the Tyrosinase Mechanism.

Fujieda, Nobutaka; Umakoshi, Kyohei; Ochi, Yuta; Nishikawa, Yosuke; Yanagisawa, Sachiko; Kubo, Minoru; Kurisu, Genji; Itoh, Shinobu

The dinuclear copper enzyme, tyrosinase, activates O2 to form a (μ‐η2:η2‐peroxido)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.

COPPER enzymes; PHENOL oxidase; CRYSTAL structure; CATECHOL; PHENOL

Angewandte Chemie, 2020, Vol 132, Issue 32, p13487

0044-8249

Academic Journal

10.1002/ange.202004733