In molecular biology, Tyrosinase refers to an oxidase, which is the rate limiting enzyme for controlling the production of melanin. It is mainly involved in two distinct reactions of melanin synthesis; firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation, as in the blackening of a peeled or sliced potato exposed to air. It is found inside melanosomes. In humans, the tyrosinase enzyme is encoded by the TYR gene.
A mutation in the tyrosinase gene resulting in impaired tyrosinase production leads to type I oculocutaneous albinism, a hereditary disorder that affects one in every 17,000 people.
Tyrosinase activity is very important. If uncontrolled during melanoma, it results in increased melanin synthesis.
Several polyphenols including flavonoids or stilbenoid, substrate analogues, free radical scavengers and copper chelators have been known to inhibit tyrosinase. Henceforth, the medical and cosmetic industries, are focusing a lot of research on tyrosinase inhibitors to treat skin disorders.
Tyrosinase carries out the oxidation of phenols such as tyrosine and dopamine using dioxygen (O2). In the presence of catechol, benzoquinone is formed (see reaction below). Hydrogens removed from catechol combine with oxygen to form water.
The substrate specificity becomes dramatically restricted in mammalian tyrosinase which utilizes only L-form of tyrosine or DOPA as substrates, and has restricted requirement for L-DOPA as cofactor.
Tyrosinases have been isolated and studied from a wide variety of plant, animal and fungal species. Tyrosinases from different species are diverse in terms of their structural properties, tissue distribution and cellular location. It has been suggested that there is no common tyrosinase protein structure occurring across all species. The enzymes found in plant, animal and fungal tissue frequently differ with respect to their primary structure, size, glycosylation pattern and activation characteristics. However, all tyrosinases have in common a binuclear type 3 copper centre within their active site. Here two copper atoms are each coordinated with three histidine residues.
Transmembrane protein and sorting
Human tyrosinase is a single membrane spanning transmembrane protein. In humans, tyrosinase is sorted into melanosomes and the catalytically active domain of the protein resides within melanosomes. Only a small enzymatically non-essential part of the protein extends into the cytoplasm of the melanocyte.
of a Streptomyces
derived tyrosinase in complex with a so called "caddie protein".
In all models only the tyrosinase molecule is shown, copper atoms are shown in green and the molecular surface is shown in red. In models D and E histidine amino acids are shown as a blue line representation. From model E it can be clearly seen that each copper atom within the active site is indeed complexed with three histidine
residues, forming a type 3 copper center
. It can also be seen from models C and D that the active site for this protein sits within a pillus formed on the molecular surface of the molecule.
The two copper atoms within the active site of tyrosinase enzymes interact with dioxygen to form a highly reactive chemical intermediate that then oxidizes the substrate. The activity of tyrosinase is similar to catechol oxidase, a related class of copper oxidase. Tyrosinases and catechol oxidases are collectively termed polyphenol oxidases.
The gene for tyrosinase is regulated by the microphthalmia-associated transcription factor (MITF).
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