Abstract

Tyrosinases have a ubiquitous presence among all domains of life. They are an essential and most vital component for pigmentation, wound healing and primary immune response. Their active site contains antiferromagnetically coupled copper ions, CuA and CuB, which is coordinated by six histidine residues. This arrangement is known as “type 3 copper centers” and is found across Tyrosinases, catecholoxidases and haemocyanins. The copper pair of Tyrosinases binds one molecule of atmospheric oxygen to catalyze two different kinds of enzymatic reactions namely the cresolase activity which is ortho-hydroxylation of monophenols and the catecholase activity oxidation of o-diphenols to o-diquinones. The formation of melanins takes place from L-tyrosine via L-dihydroxyphenylalanine (L-dopa). Since the tertiary structure of Tyrosinase has still not been elucidated, researchers have a hard time in understanding the complicated hydroxylation mechanism at the active center. Recently researchers have experimentally determined the bacterial Tyrosinase structures in Streptomyces and Bacillus, although no such attempt has been taken towards solving the structure of the human Tyrosinase protein despite of the prevailing knowledge regarding the protein. In our current work, we have tried to model the tertiary structure of the human Tyrosinase protein using template based (Homology) and non-template based (ab initio) modeling methods. We have also compared the scores of our model with that of the existing bacterial model and also tried to study its behavior using Molecular Dynamics techniques at a small scale.