Structural highlights
5m8r is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.4Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
TYRP1_HUMAN Oculocutaneous albinism type 3. The disease is caused by mutations affecting the gene represented in this entry.
Function
TYRP1_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 PubMed
Tyrosinase-related protein 1 (TYRP1) is one of three tyrosinase-like glycoenzymes in human melanocytes that are key to the production of melanin, the compound responsible for the pigmentation of skin, eye, and hair. Difficulties with producing these enzymes in pure form have hampered the understanding of their activity and the effect of mutations that cause albinism and pigmentation disorders. Herein we show that the typical tyrosinase-like subdomain of TYRP1 contains two zinc ions in the active site instead of copper ions as found in tyrosinases, which explains why TYRP1 does not exhibit tyrosinase redox activity. In addition, the structures reveal for the first time that the Cys-rich subdomain, which is unique to vertebrate melanogenic proteins, has an epidermal growth factor-like fold and is tightly associated with the tyrosinase subdomain. Our structures suggest that most albinism-related mutations of TYRP1 affect its stability or activity.
Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis.,Lai X, Wichers HJ, Soler-Lopez M, Dijkstra BW Angew Chem Int Ed Engl. 2017 Aug 7;56(33):9812-9815. doi: 10.1002/anie.201704616., Epub 2017 Jul 17. PMID:28661582[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lai X, Wichers HJ, Soler-Lopez M, Dijkstra BW. Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. Angew Chem Int Ed Engl. 2017 Aug 7;56(33):9812-9815. doi: 10.1002/anie.201704616., Epub 2017 Jul 17. PMID:28661582 doi:http://dx.doi.org/10.1002/anie.201704616
