5m8s
Crystal structure of human tyrosinase related protein 1 mutant (T391V-R374S-Y362F) in complex with phenylthiourea (PTU)
Structural highlights
DiseaseTYRP1_HUMAN Oculocutaneous albinism type 3. The disease is caused by mutations affecting the gene represented in this entry. FunctionTYRP1_HUMAN Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid. May regulate or influence the type of melanin synthesized. Also to a lower extent, capable of hydroxylating tyrosine and producing melanin.[UniProtKB:P07147] Publication Abstract from PubMedTyrosinase-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. Phenylthiourea Binding to Human Tyrosinase-Related Protein 1.,Lai X, Wichers HJ, Soler-Lopez M, Dijkstra BW Int J Mol Sci. 2020 Jan 30;21(3):915. doi: 10.3390/ijms21030915. PMID:32019241[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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