Structure and Function of Human Tyrosinase and Tyrosinase-Related Proteins

Xuelei Lai, Harry J. Wichers, Montserrat Soler-Lopez*, Bauke W. Dijkstra

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)47-55
JournalChemistry - A European Journal
Volume24
Issue number1
Early online date28 Nov 2017
DOIs
Publication statusPublished - 2 Jan 2018

Keywords

  • Albinism
  • Melanin
  • Metalloenzymes
  • Proteins
  • Tyrosinase

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