Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1)

Spritz, Richard A.; Oh, Jangsuk; Fukai, Kazuyoshi; Holmes, Stuart A.; Ho, Lingling; Chitayat, David; France, Thomas D.; Musarella, Maria A.; Orlow, Seth; Schnur, Rhonda E.; Weleber, Richard G.; Levin, Alex V.

doi:10.1002/(sici)1098-1004(1997)10:2<171::aid-humu11>3.3.co;2-9

Cited by 14 publications

(20 citation statements)

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“…In addition, the sulfur atom in methionine residues is easily oxidized to MetO or irreversibly MetO 2 . Several studies have shown that mutating a conserved Met374 in mammalian tyrosinase results in an inactive protein . This methionine (M215 in TyrBm) is highly conserved in type‐3 copper proteins, and is located 3.4‐5Å away from the second coordinating CuB histidine residue [Table and Fig.…”

Section: A Conserved Methionine Residuementioning

confidence: 99%

Structure–function correlations in tyrosinases

2015

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Tyrosinases are metalloenzymes belonging to the type-3 copper protein family which contain two copper ions in the active site. They are found in various prokaryotes as well as in plants, fungi, arthropods, and mammals and are responsible for pigmentation, wound healing, radiation protection, and primary immune response. Tyrosinases perform two sequential enzymatic reactions: hydroxylation of monophenols and oxidation of diphenols to form quinones which polymerize spontaneously to melanin. Two other members of this family are catechol oxidases, which are prevalent mainly in plants and perform only the second oxidation step, and hemocyanins, which lack enzymatic activity and are oxygen carriers. In the last decade, several structures of plant and bacterial tyrosinases were determined, some with substrates or inhibitors, highlighting features and residues which are important for copper uptake and catalysis. This review summarizes the updated information on structure-function correlations in tyrosinases along with comparison to other type-3 copper proteins.

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Section: A Conserved Methionine Residuementioning

confidence: 99%

Structure–function correlations in tyrosinases

2015

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“…Melanin is ubiquitous.T he high-molecular-weight pigment is involved in the coloring of skin and hairs, [1][2][3] protection against UV and ionizing radiation, [4][5][6] immunological defense, [7,8] and other important biological functions. [9][10][11][12][13] It is formed by the polymerization of dopaquinone,w hich is generated by monooxygenation of tyrosine,inturn mediated by the enzyme tyrosinase (TY).…”

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confidence: 99%

Tyrosinase versus Catechol Oxidase: One Asparagine Makes the Difference

2016

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Tyrosinases mediate the ortho-hydroxylation and two-electron oxidation of monophenols to ortho-quinones. Catechol oxidases only catalyze the oxidation of diphenols. Although it is of significant interest, the origin of the functional discrimination between tyrosinases and catechol oxidases has been unclear. Recently, it has been postulated that a glutamate and an asparagine bind and activate a conserved water molecule towards deprotonation of monophenols. Here we demonstrate for the first time that a polyphenoloxidase, which exhibits only diphenolase activity, can be transformed to a tyrosinase by mutation to introduce an asparagine. The asparagine and a conserved glutamate are necessary to properly orient the conserved water in order to abstract a proton from the monophenol. These results provide direct evidence for the crucial importance of a proton shuttle for tyrosinase activity of type 3 copper proteins, allowing a consistent understanding of their different chemical reactivities.

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“…However, in white populations, the spectrum and proportion of TYR mutations are very different. Missense mutations at the amino acid position 299 accounted for less than 1% of all reported OCA1 missense mutant alleles 12,19 . It appears that mutations at codon 299 are more frequent in Chinese population, suggesting an ethnic difference in the spectrum of OCA1 mutations.…”

Section: Discussionmentioning

confidence: 95%

“…the hydroxylation of tyrosine to dihydroxyphenylalanine (DOPA) and the subsequent dehydrogenation of DOPA to dopaquinone 6 . More than 210 mutations (Albinism Database and Human Gene Mutation Database, http://albinismdb.med.umn.edu) in the TYR gene have been reported to cause OCA1 in various ethnic groups 7–15 . However, less than 10 of these mutations have been reported in Chinese populations 7–9 .…”

Section: Introductionmentioning

confidence: 99%