D-dopachrome decarboxylase

D-dopachrome decarboxylase

The crystal structure of D-dopachrome decarboxylase.

D-dopachrome decarboxylase (DDDC) is an enzyme that plays a crucial role in the melanin biosynthesis pathway. It is responsible for the conversion of D-dopachrome into 5,6-dihydroxyindole (DHI), a key intermediate in the production of eumelanin. DDDC is found in various organisms, including bacteria, fungi, plants, and animals.

Function

DDDC catalyzes the decarboxylation of D-dopachrome, a product of the enzymatic oxidation of L-tyrosine, to form DHI. This reaction is a vital step in the synthesis of eumelanin, a pigment responsible for the dark coloration of skin, hair, and eyes in humans and other animals. DHI serves as a precursor for the subsequent enzymatic reactions leading to the production of eumelanin.

Structure

The crystal structure of DDDC has been extensively studied, revealing important insights into its catalytic mechanism. DDDC is a homodimeric enzyme, with each monomer consisting of two domains: an N-terminal domain and a C-terminal domain. The active site, where the decarboxylation reaction takes place, is located at the interface between the two monomers.

Role in Melanoma

Melanoma is a type of skin cancer that arises from the uncontrolled growth of melanocytes, the cells responsible for producing melanin. DDDC has been implicated in the progression of melanoma, as its activity is often upregulated in melanoma cells compared to normal melanocytes. Inhibition of DDDC has shown promise as a potential therapeutic strategy for the treatment of melanoma.