Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 561621
Title Phenylthiourea binding to human tyrosinase-related protein 1
Author(s) Lai, Xuelei; Wichers, Harry J.; Soler-Lopez, Montserrat; Dijkstra, Bauke W.
Source International Journal of Molecular Sciences 21 (2020)3. - ISSN 1661-6596
DOI https://doi.org/10.3390/ijms21030915
Department(s) Food, Health & Consumer Research
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2020
Keyword(s) Albinism - Crystal structure - Human tyrosinase - Human tyrosinase-related protein - Inhibitor - Melanogenesis - N-glycosylation - Phenylthiourea - Zinc-Copper enzymes
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.

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