Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Enzymes. 2024;56:31-54. doi: 10.1016/bs.enz.2024.05.001. Epub 2024 May 24.
Tyrosinases (TYR) play a key role in melanin biosynthesis by catalyzing two reactions: monophenolase and diphenolase activities. Despite low amino acid sequence homology, TYRs from various organisms (from bacteria to humans) have similar active site architectures and catalytic mechanisms. The active site of the TYRs contains two copper ions coordinated by histidine (His) residues. The catalytic mechanism of TYRs involves electron transfer between copper sites, leading to the hydroxylation of monophenolic compounds to diphenols and the subsequent oxidation of these to corresponding dopaquinones. Although extensive studies have been conducted on the structure, catalytic mechanism, and enzymatic capabilities of TYRs, some mechanistic aspects are still debated. This chapter will delve into the structure of the active site, catalytic function, and inhibition mechanism of TYRs. The goal is to improve our understanding of the molecular mechanisms underlying TYR activity. This knowledge can help in developing new strategies to modulate TYR function and potentially treat diseases linked to melanin dysregulation.
酪氨酸酶（TYR）通过催化两个反应在黑色素生物合成中发挥关键作用：单酚酶和二酚酶活性。尽管氨基酸序列同源性低，但来自各种生物体（从细菌到人类）的 TYRs 具有相似的活性位点结构和催化机制。TYRs 的活性位点包含两个由组氨酸（His）残基配位的铜离子。TYRs 的催化机制涉及铜位点之间的电子转移，导致单酚化合物羟化为二酚，随后将这些二酚氧化为相应的多巴醌。尽管对 TYRs 的结构、催化机制和酶学特性进行了广泛的研究，但一些机制方面仍存在争议。本章将深入探讨 TYRs 的活性位点结构、催化功能和抑制机制。目标是提高我们对 TYR 活性的分子机制的理解。这一知识可以帮助我们开发调节 TYR 功能的新策略，并有可能治疗与黑色素失调相关的疾病。
