Copper–Oxygen Dynamics in the Tyrosinase Mechanism. Issue 32 (26th May 2020)

• Record Type: Journal Article
• Authors: Fujieda, Nobutaka; Umakoshi, Kyohei; Ochi, Yuta; Nishikawa, Yosuke; Yanagisawa, Sachiko; Kubo, Minoru; Kurisu, Genji; Itoh, Shinobu
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 32(2020)
• Page Start: 13385
• Page End: 13390
• Publication Date: 2020-05-26
• Subjects: active site dynamics -- copper -- copper enzymes -- dioxygen activation -- tyrosinase; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202004733
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The dinuclear copper enzyme, tyrosinase, activates O2 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. Abstract : Let's Cu move : The dinuclear copper enzyme, tyrosinase, activates O2 and hydroxylates phenols to catechols. Substrate binding is shown to induce a rearrangement of the copper–oxygen species for hydroxylation of aromatic C−H bond. A copper center migrates (CuA1→CuA2) activating the bound substrate as well as the dioxygen molecule that is between the copper centers.