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Structure and Function of Human Tyrosinase and Tyrosinase‐Related Proteins
Author(s) -
Lai Xuelei,
Wichers Harry J.,
SolerLopez Montserrat,
Dijkstra Bauke W.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704410
Subject(s) - tyrosinase , melanin , mutagenesis , homology modeling , enzyme , function (biology) , biochemistry , biology , protein structure , amino acid , albinism , structural biology , computational biology , genetics , gene , mutation
Abstract Melanin is the main pigment responsible for the color of human skin, hair and eye. Its biosynthesis requires three melanogenic enzymes, tyrosinase (TYR), and the tyrosinase‐related proteins TYRP1 and TYRP2. The difficulty of isolating pure and homogeneous proteins from endogenous sources has hampered their study, and resulted in many contradictory findings regarding their physiological functions. In this review, we summarize recent advances on the structure and function of TYR and TYRPs by virtue of the crystal structure of human TYRP1, which is the first available structure of a mammalian melanogenic enzyme. This structure, combined with tyrosinase structures from other lower eukaryotes and mutagenesis studies of key active site residues, sheds light on the mechanism of TYR and TYRPs. Furthermore, a TYRP1‐based homology model of TYR provides a high‐quality platform to map and analyze albinism‐related mutations, as well as the design of specific antimelanogenic compounds. Finally, we provide perspectives for future structure/function studies of TYR and TYRPs.