Title : Structure of
Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis
Abstract :
- 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
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 3. TYRP1, subdomain
- 3. tyrosinase, subdomain
- 4. tyrosinase, subdomain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):