Histidine Residues at the Copper-binding Site in Human Tyrosinase Are Essential for Its Catalytic Activities

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2020 Mar 18

PMID 32180482

Citations 20

Authors

Hyangsoon Noh

Sung Jun Lee

Hyun-Joo Jo

Hye Won Choi

Sungguan Hong

Kwang-Hoon Kong

Affiliations

Soon will be listed here.

Abstract

Tyrosinase is a copper-binding enzyme involved in melanin biosynthesis. However, the detailed structure of human tyrosinase has not yet been solved, along with the identification of the key sites responsible for its catalytic activity. We used site-directed mutagenesis to identify the residues critical for the copper binding of human tyrosinase. Seven histidine mutants in the two copper-binding sites were generated, and catalytic activities were characterised. The tyrosine hydroxylase activities of the CuA site mutants were approximately 50% lower than those of the wild-type tyrosinase, while the dopa oxidation activities of the mutants were not significantly different from that of wild-type tyrosinase. By contrast, mutations at CuB significantly decreased both tyrosine hydroxylation and dopa oxidation activities, confirming that the catalytic sites for these two activities are at least partially distinct. These findings provide a useful resource for further structural determination and development of tyrosinase inhibitors in the cosmetic and pharmaceutical industries.

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