tyrosinase

Tyrosinase (oculocutaneous albinism IA)
Identifiers
Symbols	TYR; OCA1A; OCAIA
External IDs	OMIM: 606933 MGI: 98880 HomoloGene: 30969
EC number	1.14.18.1
Gene ontology Molecular function • monooxygenase activity • monophenol monooxygenase activity • copper ion binding • protein binding • protein homodimerization activity • metal ion binding • protein heterodimerization activity Cellular component • cytoplasm • lysosome • Golgi-associated vesicle • membrane • integral to membrane • melanosome • perinuclear region of cytoplasm Biological process • melanin biosynthetic process from tyrosine • eye pigment biosynthetic process • visual perception • sensory perception of sound • metabolic process • pigmentation
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7299	22173
Ensembl	ENSG00000077498	ENSMUSG00000004651
UniProt	P14679	Q3UFK9
RefSeq	NM_000372 (mRNA)	NM_011661 (mRNA)
	NP_000363 (protein)	NP_035791 (protein)
Location	Chr 11: 88.55 - 88.67 Mb	Chr 7: 87.3 - 87.37 Mb
PubMed search	[1]	[2]

Tyrosinase (monophenol monooxygenase) (EC 1.14.18.1; CAS number: 9002-10-2) is an enzyme that catalyses the oxidation of phenols (such as tyrosine) and is widespread in plants and animals. 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.

Pathology

A mutation in the tyrosinase gene resulting in impaired tyrosinase production results in type I oculocutaneous albinism, a hereditary disease that one in every 17,000 person has in the United States.

Chemical reactions

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.

Catechol-Quinone

The substrate specificity become 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.^[1]

Tyrosinase structure

Tyrosinases have been isolated and studied from a wide variety of plant, animal and fungi species. Tyrosinases from different species are diverse in terms of their structural properties, tissue distribution and cellular location.^[2] It has been suggested that there is no common tyrosinase protein structure occurring across all species.^[3] The enzymes found in plant, animal and fungi 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.^[4] In humans, tyrosinase is sorted into melanosomes^[5] 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.

Active site

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.

Crystallographic structure of a Streptomyces derived tyrosinase in complex with a so called "caddie protein".^[6] 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.

Gene regulation

The gene for Tyrosinase is regulated by the Microphthalmia-associated transcription factor^[7][8].

References

External links

• MeSH Tyrosinase