Research Work

Tyrosinase is the key rate-limiting enzyme in the melanin biosynthesis pathway. Melanin acts as a protective barrier against UV radiations, free radicals, gamma rays, etc., thus, the mechanism of melanin biosynthesis needs to be studied in order to design a therapeutic approach for its regulation. The major bottleneck in this study is the difficulty in expressing the Tyrosinase protein in its native form due to six or seven N-glycosylation regions, each of which has a distinctive role in the enzyme function. The Tyrosinase has a trans-membrane region that adds up to the complexity of getting pure crystals for the structure elucidation. However, with the development of the techniques like single-particle cryo-electron microscopy (Cryo-EM), the field of structural biology has seen a resolution revolution from the mainstream approaches like X-ray crystallography.

The defects in melanin biosynthesis can lead to several disorders related to hypopigmentation and hyperpigmentation in the skin and are associated with the risk of melanoma, one of the major causes of skin cancer-related deaths globally. In this work, efforts will be made to fill the gaps in understanding the structure of the human Tyrosinase enzyme and its catalytic mechanism by developing a suitable expression system in a mammalian cell line and employing advanced techniques like Cryo-EM.