Phenylthiourea binding to human tyrosinase-related protein 1

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Tyrosinase-related protein 1 (TYRP1) is one of the three human melanogenic enzymes involved in the biosynthesis of melanin, a pigment responsible for the color of the skin, hair, and eyes. It shares high sequence identity with tyrosinase, but has two zinc ions in its active site rather than two copper ions as in tyrosinase. Typical tyrosinase inhibitors do not directly coordinate to the zinc ions of TYRP1. Here, we show, from an X-ray crystal structure determination, that phenylthiourea, a highly potent tyrosinase inhibitor, does neither coordinate the active site zinc ions, but binds differently from other structurally characterized TYRP1-inhibitor complexes. Its aromatic ring is directed outwards from the active site, apparently as a result from the absence of polar oxygen substituents that can take the position of water molecules bound in the active site. The compound binds via hydrophobic interactions, thereby blocking substrate access to the active site.

Original languageEnglish
Article number915
JournalInternational Journal of Molecular Sciences
Volume21
Issue number3
DOIs
Publication statusPublished - 1 Feb 2020

Keywords

  • Albinism
  • Crystal structure
  • Human tyrosinase
  • Human tyrosinase-related protein
  • Inhibitor
  • Melanogenesis
  • N-glycosylation
  • Phenylthiourea
  • Zinc-Copper enzymes

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