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Tyrosinase (oculocutaneous albinism IA)
Identifiers
Symbols TYR; OCA1A; OCAIA
External IDs OMIM606933 MGI98880 HomoloGene30969 GeneCards: TYR Gene
EC number 1.14.18.1
RNA expression pattern
PBB GE TYR 206630 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7299 22173
Ensembl ENSG00000077498 ENSMUSG00000004651
UniProt P14679 Q3UFK9
RefSeq (mRNA) NM_000372 NM_011661
RefSeq (protein) NP_000363 NP_035791
Location (UCSC) 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.

Contents

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 fungal 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 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.

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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

  1. ^ Hearing VJ, Ekel TM, Montague PM, Nicholson JM (February 1980). "Mammalin tyrosinase. Stoichiometry and measurement of reaction products". Biochim. Biophys. Acta 611 (2): 251–68. PMID 6766744. 
  2. ^ Mayer, AM (2006). "Polyphenol oxidases in plants and fungi: Going places? A review". Phytochemistry 67: 2318–2331. doi:10.1016/j.phytochem.2006.08.006. PMID 16973188. 
  3. ^ Jaenicke, E and Decker, H. (2003). "Tyrosinases from crustaceans form hexamers". Biochem. J. 371: 515–523. doi:10.1042/BJ20021058. PMID 12466021. 
  4. ^ Kwon BS, Haq AK, Pomerantz SH, Halaban R (November 1987). "Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus". Proc. Natl. Acad. Sci. U.S.A. 84 (21): 7473–7. doi:10.1073/pnas.84.21.7473. PMID 2823263. PMC 299318. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2823263. 
  5. ^ Theos AC, Tenza D, Martina JA, Hurbain I, Peden AA, Sviderskaya EV, Stewart A, Robinson MS, Bennett DC, Cutler DF, Bonifacino JS, Marks MS, Raposo G (November 2005). "Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes". Mol. Biol. Cell 16 (11): 5356–72. doi:10.1091/mbc.E05-07-0626. PMID 16162817. 
  6. ^ PDB 1WX3; Matoba Y, Kumagi, T. et al. (2006). "Crystallographic evidence that the dinuclear copper center of tyrosinase is flexible during catalysis". J. Biol. Chem. 281 (13): 8981–8990. doi:10.1074/jbc.M509785200. PMID 16436386. 
  7. ^ Hou L, Panthier JJ, Arnheiter H (2000). "Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF". Development 127 (24): 5379–89. PMID 11076759. 
  8. ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. 

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