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evolution
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Ms1 genome scaffolds with publicly available Streptomyces genus whole genome sequences show the highest nucleotide identity (99%) with Streptomyces cyaneofuscatus strain NRRL B-2570, genes melC1 and melC2
evolution
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the enzyme belongs to the type-3 copper protein family
evolution
the primary sequence of Aspergillus niger PA2 tyrosinase has approximately 99% identity with that of Aspergillus niger CBS 513.88, phylogenetic analysis. Tyrosinase belongs to a large group of proteins termed as type-3 copper proteins
evolution
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tyrosinases and catechol oxidases (EC 1.10.3.1) are members of the class of type III copper enzymes. While tyrosinases accept both mono- and o-diphenols as substrates, only the latter substrate is converted by catechol oxidases. The distinction between mono- and diphenolase activity does not depend on the degree of restriction of the active site, and thus a more important role for amino acid residues located at the entrance to and in the second shell of the active site is proposed
evolution
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tyrosinases are widespread in nature and act on a range of substrates
evolution
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the primary sequence of Aspergillus niger PA2 tyrosinase has approximately 99% identity with that of Aspergillus niger CBS 513.88, phylogenetic analysis. Tyrosinase belongs to a large group of proteins termed as type-3 copper proteins
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malfunction
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after 72 h of treatment with inhibitors acetazolamide and kojic acid, acetazolamide at 0.04 mM significantly decreases the embryos pigmentation to 40.8% of untreated embryos, while kojic acid at 0.04 mM decreases only 25.0% of pigmentation. Phenotype, overview
malfunction
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enzyme inhibition reduces melanogenesis
malfunction
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excessive accumulation of melanin, due to the overexpression of the enzyme, leads to skin disorders such as age spots, freckles and malignant melanoma
malfunction
mutations in the tyrosinase gene cause oculocutaneous albinism type 1 (OCA1), an autosomal recessive disease associated with reduced melanin pigment in the hair, skin, and eyes and decreased quality of vision
malfunction
oculocutaneous albinism Type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 exxist, severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. The recombinant OCA1A mutants expressed in insect cells show very low protein expression, protein yield, and are enzymatically inactive, while mutants mimicking OCA1B are biochemically similar to the wild-type, but exhibit lower specific activities and protein stabilities than the wild-type enzyme. OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactive tyrosinase and results in OCA1B albinism
malfunction
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silencing of walnut tyrosinase (jrTYR) induces a lesion mimic phenotype in walnut leaves, presumably owing to tyramine-mediated cell death
malfunction
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the reduction of tyrosinase activity associated with the knockdown of membrane-associated transporter protein, MATP, using siRNA is readily recovered by copper treatment in the in vitro L-DOPA oxidase activity assay of tyrosinase. N-glycosylation is an important factor for tyrosinase activity, which was reduced in the MATP-knockdown cells
malfunction
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with 95% reduction in catechol oxidase activity relative to wild-type controls, the plants develop a phenotype with disease-like necrotic lesions. Levels of salicylic acid, H2O2, or malondialdehyde are not significantly different in the PPO-silenced leaves compared to wild-type leaves. Metabolomic analysis of PPO-silenced and wild-type leaves reveal significant differences in many metabolites, particularly phenylpropanoids, and about 10fold increased levels of tyramine. Although L-DOPA is undetectable in both PPO-silenced and wild-type walnut plants, levels of dopamine (derived from either L-DOPA or tyramine) and 5,6 dihydroxyindole (derived from L-DOPA) are reduced approximately 6 and 100fold, respectively, in PPO-silenced plants relative to wild-type controls
metabolism
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PPO-mediated conversion of tyrosine to L-DOPA, tyrosine metabolism in walnut, pathway overview
metabolism
substrate specificity allows elucidation of a likely mechanism of aurone formation from 2,4,6,4-tetrahydroxychalcone or PHC involving both tyrosinase and catechol oxidase activities of the Antirrhinum majus PPO, pathway overview. Starting with THC, tyrosinase and catechol oxidase activity result in 3-hydroxylation and formation of the corresponding o-quinone. Besides aurone synthase PPO, a cytochrome P450 chalcone 3-hydroxylase is also involved in the 3-hydroxylation step
metabolism
substrate specificity allows elucidation of a likely mechanism of aurone formation from 2,4,6,4-tetrahydroxychalcone or PHC involving both tyrosinase and catechol oxidase activities of the Antirrhinum majus PPO, pathway overview. Starting with THC, tyrosinase and catechol oxidase activity result in 3-hydroxylation and formation of the corresponding o-quinone. Whether aureusidine synthase PPO carries out the 3-hydroxylation reaction in vivo, or whether a cytochrome P450 chalcone 3-hydroxylase is also involved is not definitively established. Aureusidine synthase, EC 1.21.3.6, likely forms the same quinone from 2',3,4,4',6'-pentahydroxychalcone without the need for the 3-hydroxylation step. The resulting quinone is predicted to undergo a 2-step non-enzyme mediated rearrangement to form aureusidine
metabolism
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the enzyme is involved in the first step in betalain biosynthesis, the conversion of tyrosine into L-DOP, i.e. L-3,4-dihydroxyphenylalanine. The resulting L-DOPA can be a substrate for DOPA 4,5-dioxygenase (DODA) that cleaves the aromatic ring to form 4,5-seco-DOPA. The cleavage product spontaneously rearranges to form betalamic acid, which can condense with amino acids or other amine groups to form yellow betaxanthins. Condensation of betalamic acid with cyclo-DOPA forms the red betacyanin pigments. The catechol oxidase activity of PPO is involved in the oxidation of DOPA to DOPA quinone that can spontaneously rearrange to form the cyclo-DOPA moiety of the red betacyanin betalains, pathway overview
metabolism
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the enzyme is involved in the melanin biosynthesis, pathway overview
metabolism
the tyrosinase activity of PPO is involved in biosynthesis of 8-8'-linked lignans, e.g. nordihydroguaiaretic acid (NDGA), in creosote bush, pathway overview
metabolism
tyrosinase catalyzes the first two steps of the melanin synthesis pathway: hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine, L-DOPA, monophenolase or cresolase activity, EC1.14.18.1, and the subsequent oxidation of L-DOPA to dopaquinone, diphenol oxidase or catecholase activity, EC 1.10.3.1
metabolism
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tyrosinase is a key enzyme in melanogenesis. The catalysis of L-tyrosine to L-dopa is the rate-limiting step of the enzymatic pathway in melanin formation
metabolism
tyrosinase is a key enzyme in melanogenesis. The catalysis of L-tyrosine to L-dopa is the rate-limiting step of the enzymatic pathway in melanin formation
metabolism
tyrosinase is a key enzyme involved in the melanin biosynthesis
metabolism
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tyrosinase is a rate-limiting enzyme for controlling the production of melanin. The melanogenesis begins with the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase (TYR). The regulation of the TYR activity is directly connected with melanin biosynthesis
metabolism
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tyrosinase is responsible for the two initial enzymatic steps in the conversion of tyrosine to melanin
metabolism
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tyrosinase is a key enzyme involved in the melanin biosynthesis
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physiological function
key enzyme involved in melanin formation
physiological function
knockdown of As-pro-PO III expression in pupae using double-stranded RNA results in high pupal mortality and deformed adults that subsequently died following emergence
physiological function
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tyrosinases are essential enzymes in melanin biosynthesis and therefore responsible for pigmentation of skin and hair
physiological function
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tyrosinases are essential enzymes in melanin biosynthesis and therefore responsible for pigmentation of skin and hair
physiological function
tyrosinases might play a significant role during egg shell formation in Schistosoma japonicum
physiological function
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phenoloxidase can serve as a protecting agent against environmental pathogens in Dugesia japonica
physiological function
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tyrosinase is a key enzyme in the melanin biosynthesis
physiological function
human tyrosinase is the first enzyme of the multistep process of melanogenesis. It catalyzes the hydroxylation of L-tyrosine to L-dihydroxyphenylalanine and the following oxidation of o-diphenol to the corresponding quinone, L-dopaquinone
physiological function
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in plants, PPO is predominantly located in the chloroplast thylakoid membranes, and its phenolic substrates are mainly located in the vacuoles but, following any treatment that damages the cells, the enzyme and substrates may come into contact, leading to rapid oxidation of the phenols
physiological function
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membrane-associated transporter protein, MATP, may play an important role in regulating tyrosinase activity via controlling melanosomal pH
physiological function
mushroom tyrosinase-associated lectin-like protein (MtaL) binds to mature Agaricus bisporus tyrosinase in vivo, binding structure analysis, overview. MtaL undergoes conformational changes upo tyrosinase binding, but the general beta-trefoil fold is conserved, it is essential for carbohydrate interaction in other lectin-like proteins. o-Quinones are precursors for the synthesis of melanins, which are pigments that play important roles in the survival of organisms
physiological function
polyphenol oxidase (PPO) is a type-3 copper enzyme catalyzing the oxidation of phenolic compounds to their quinone derivates, which are further converted to melanin, a ubiquitous pigment in living organisms
physiological function
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polyphenoloxidases (PPO) of the type-3 copper protein family are considered to be catecholoxidases catalyzing the oxidation of o-diphenols to their corresponding quinones
physiological function
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PPOs have a role in postharvest browning, secondary reactions of PPO-generated o-quinones with cellular nucleophiles leading to the familiar discoloration of fresh products and plant materials
physiological function
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PPOs have a role in postharvest browning, secondary reactions of PPO-generated o-quinones with cellular nucleophiles leading to the familiar discoloration of fresh products and plant materials
physiological function
PPOs have a role in postharvest browning, secondary reactions of PPO-generated o-quinones with cellular nucleophiles leading to the familiar discoloration of fresh products and plant materials
physiological function
PPOs have a role in postharvest browning, secondary reactions of PPO-generated o-quinones with cellular nucleophiles leading to the familiar discoloration of fresh products and plant materials. Aurones (aureusidin and bracteatin) are formed from 2,4,6,4-tetrahydroxychalcone or 2,4,6,3,4-pentahydroxychalcone upon incubation with extracts of yellow snapdragon flowers through activity of aureusidin (or aurone) synthase, EC 1.21.3.6
physiological function
PPOs have a role in postharvest browning, secondary reactions of PPO-generated o-quinones with cellular nucleophiles leading to the familiar discoloration of fresh products and plant materials. Aurones (aureusidin and bracteatin) are formed from 2,4,6,4-tetrahydroxychalcone or 2,4,6,3,4-pentahydroxychalcone upon incubation with extracts of yellow snapdragon flowers through activity of aureusidin (or aurone) synthase.
physiological function
the enzyme catalyzes the oxidation of L-tyrosine (monophenol substrate) and L-3,4-dihydroxyphenylalanine (L-DOPA, diphenol substrate) to form dopaquinone. The monophenolase and diphenol oxidase activities are linked to the tyrosinase active site, which is composed of six histidine residues that coordinate two copper ions (CuA and CuB) essential for activity
physiological function
the enzyme is involved in browning of fruit slices
physiological function
the enzyme is responsible for the browning of fruits, vegetables, fungi and crustaceans and is essential in the melanogenesis process of human skin pigmentation for protection from UV-induced damage. Nevertheless, its excessive accumulation can produce hyperpigmentation disorders such as freckles, solar lentigines, ephelide, and melasma
physiological function
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tyrosinase (TYR) is a key enzyme in melanin biosynthesis and its activity is an important biomarker for dermatological disorders, such as vitiligo, melanoma and actinic damages
physiological function
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tyrosinase catalyzes the reactions that provide the starting material for melanin biosynthesis, namely the ortho-hydroxylation of monophenols to o-diphenols (monophenolase activity, EC 1.14.18.1) and the subsequent oxidation of o-diphenols to the corresponding o-quinones (diphenolase activity, EC 1.10.3.1), which are both coupled to the reduction of molecular oxygen to water. During the catalytic cycle, the dinuclear copper center passes through three different oxidation states. In the resting met form, the copper atoms (CuII) are bridged by a hydroxide ion or water molecule. The deoxy form represents the reduced (CuI) state, which is converted into the reactive oxy form upon oxygen binding
physiological function
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tyrosinase has a primary role in the reaction by oxidation of tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) and dopaquinone in the biosynthetic pathway of melanin formation
physiological function
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tyrosinase is a copper-containing enzyme widely distributed in nature, where it catalyses two types of reaction: (a) the ortho-hydroxylation of monophenols (L-tyrosine) to o-diphenols (L-dopa), monophenolase activity, and (b) the oxidation of o-diphenols (L-dopa) to o-quinones (L-dopaquinone), diphenolase activity. Both types of reaction require molecular oxygen as the second substrate of the enzyme. The o-dopaquinone produced from L-tyrosine and L-dopa rapidly evolves to dopachrome
physiological function
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tyrosinase is a key enzyme in melanin synthesis
physiological function
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tyrosinase is a key enzyme in melanogenesis, which is essential for pigmentation. The catalysis of L-tyrosine to L-dopa is the rate-limiting step of the enzymatic pathway in melanin formation. Tyrosinase is also an important factor in wound healing and cuticle formation in arthropods and browning in plants
physiological function
tyrosinase is a key enzyme in melanogenesis, which is essential for pigmentation. The catalysis of L-tyrosine to L-dopa is the rate-limiting step of the enzymatic pathway in melanin formation. Tyrosinase is also an important factor in wound healing and cuticle formation in arthropods and browning in plants
physiological function
tyrosinase is a key enzyme involved in the melanin biosynthesis
physiological function
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tyrosinase is a multifunctional copper-containing metalloenzyme that is critical for melanin pigment production anddetoxification of phenol compounds. The catalytic roles of tyrosinase include multifunctional distinctions such as hydroxylaseand oxidase functions, and tyrosinase possesses catalase, peroxygenase, phenolase, and catecholase activities
physiological function
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tyrosinase is a multifunctional copper-containing oxygenase and catalyzes the hydroxylation of a monophenol and the conversion of o-diphenols to the corresponding o-quinones. These quinones are highly reactive compounds that can polymerize spontaneously to form melanin. Products formed as a result of tyrosinase activity are precursors for skin pigmentation, defense, and protective mechanisms in fungi
physiological function
tyrosinase is the first enzyme of the multistep process of melanogenesis. It catalyzes the hydroxylation of L-tyrosine to L-dihydroxyphenylalanine and the following oxidation of o-diphenol to the corresponding quinone, L-dopaquinone
physiological function
tyrosinases are an ubiquitous group of copper-containing metalloenzymes that hydroxylate and oxidize phenolic molecules. Tyrosinase catalyzes the o-hydroxylation of monophenols (EC 1.14.18.1) and the oxidation of o-diphenols (cf. EC 1.10.3.1)
physiological function
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tyrosinases are enzymes that exhibit both monooxygenase and oxidase activity and both activities arise from the binding of dioxygen to the two copper atoms (usually identified as CuA and CuB) located in the active site
physiological function
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key enzyme involved in melanin formation
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physiological function
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tyrosinase is a key enzyme involved in the melanin biosynthesis
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additional information
Cu2+ existing in the active centre of PPOs is likely to be dissociated in relatively extreme acid environment, and might form the precipitate of copper hydroxide in relatively extreme alkaline environment
additional information
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determination of tyrosinase substrate-binding modes, overview. Both monophenol hydroxylation and diphenol oxidation occur at the same site. Compared to tyrosinase, the concurrent presence of a phenylalanine above the active site and a restricting thioether bond on the histidine coordinating copper ion CuA prevent hydroxylation of monophenols by catechol oxidases, EC 1.10.3.1. A conserved water molecule activated by E195 and N205 is proposed to mediate deprotonation of the monophenol at the active site. The diphenol L-dopa binds to uinc ion ZnA in the active site in the same orientation as tyrosine, assisted by interactions with H208, both the hydroxylation and oxidation activities occur without significant binding site reorganization. Comarison of binding modes of catecol oxidase/diphenolase, and tyrosinase/monophenolase. Structure-supported monophenol hydroxylation and deprotonation mechanism, overview
additional information
during the catalytic reaction, the type-3 copper center of tyrosinase exists in three different states. The reduced deoxy state [Cu(I)-Cu(I)] binds molecular oxygen and results in the oxy state [Cu(II)-O2 2-Cu(II)]. In the oxy state, peroxide is bound in a l-g2:g2 bridging mode. The met state [Cu(II)-Cu(II)] is assumed as the resting state of the copper site, where Cu(II) ions are bridged by a water molecule or hydroxyl ion. After addition of two equivalents H2O2 the full oxy form of the tyrosinase is developed
additional information
enzyme active domain structure, modeling, overview
additional information
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enzyme active domain structure, modeling, overview
additional information
homology model of human tyrosinase incorporated into the phospholipid membrane, overview
additional information
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homology model of human tyrosinase incorporated into the phospholipid membrane, overview
additional information
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homology modeling of the enzyme sructure using the crystal structure of bacterial tyrosinase from Bacillus megaterium as template, PDB ID 3NQ1
additional information
homology modeling of the enzyme sructure using the crystal structure of bacterial tyrosinase from Bacillus megaterium as template, PDB ID 3NQ1
additional information
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homology modeling of the enzyme sructure using the crystal structure of bacterial tyrosinase from Bacillus megaterium as template, PDB ID 3NQ1
additional information
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molecular docking and molecular dynamic simulation
additional information
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molecular docking and molecular dynamic simulation
additional information
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molecular dynamic analysis indicate that the hydroxyl group of monophenolic substrates can bind to copper ion CuA after the flexible but sterically hindering Phe259 swings away on a picosecond time scale. The hydroxide is replaced by a peroxide ion bridging CuA with CuB. The substrate 4-coumaric acid is orientated in a similar position as described previously for tyrosine which hydroxylic oxygen is pointing to the free coordination point above CuA and the phenolic ring was in a Pi-Pi interaction with the imidazol ring of His243, molecular dynamic simulations, overview
additional information
molecular dynamic computational simulations of tyrosinase and the interaction of beta-arbutin, deoxyarbutin and their o-diphenol products with tyrosinase show how these ligands bind at the copper centre of tyrosinase, using enzyme crystal structure, PDB ID 2Y9W. The presence of an energy barrier in the release of the o-diphenol product of deoxyarbutin, which is not present in the case of beta-arbutin, together with the differences in polarity and, consequently differences in their interaction with water explain the differences in the kinetic behaviour of both compounds. The release of the o-diphenol product of deoxyarbutin from the active site might be slower than in the case of beta-arbutin, contributing to its oxidation to a quinone before being released from the protein into the water phase. Computational simulations of o-diphenol binding
additional information
structure homology modeling of wild-type an dmutant enzymes
additional information
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structure homology modeling of wild-type an dmutant enzymes
additional information
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the enzyme shows monophenolase/diphenolase specificity, structure-function relationship analysis, overview. Enzyme jrTYR contains the well-conserved tyrosinase CXXC motif (C88 A-Y-C91), which has been reported to be crucial for copper uptake. Active site structure analysis
additional information
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the inter-relationship of the four discrete oxidation states of tyrosinase, i.e. oxy, deoxy, met, and deact, detailed overview. Native tyrosinase occurs mainly as met-tyrosinase in which a hydroxyl ion is bound to the two copper ions. Phenols bind to met-tyrosinase but are not oxidised by this form of the enzyme. Catechols, however, are oxidised by met-tyrosinase which in the process is reduced to deoxy-tyrosinase in which both coppers are now in the Cu(I) oxidation state. Deoxy-tyrosinase rapidly binds dioxygen to give oxy-tyrosinase in which the two oxygen atoms are held between the copper ions in the active site. Oxy-tyrosinase is the primary oxidising form of the enzyme and oxidises phenols by a monooxygenase mechanism and oxidises catechols by an oxidase mechanism. Thus, in the presence of dioxygen both phenols and catechols are oxidised by oxy-tyrosinase to ortho-quinones by quite separate oxidative cycles. During the catecholic cycle a catechol is occasionally treated as a phenol and oxidised by oxy-tyrosinase by a monooxygenase mechanism leading to the irreversible formation of deact-tyrosinase in which one of the copper atoms is reduced to the Cu(0) state and may diffuse out of the active centre. This minor pathway eventually leads to total inactivation of the enzyme by catechols. Oxy- to deact-tyrosinase conversion is inactivated by catechols and resorcinols
additional information
tyrosinase has a di-copper active site, homology modeling using crystal structure PDB ID 3W6W as template. The L-tyrosine-binding residues of tyrosinase active site pocket are highly conserved
additional information
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tyrosinase has a di-copper active site, homology modeling using crystal structure PDB ID 3W6W as template. The L-tyrosine-binding residues of tyrosinase active site pocket are highly conserved
additional information
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tyrosinase is a kind of multiple functional oxidase containing di-copper catalytic core
additional information
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tyrosinase needs 3,4-dihydroxyphenylalanine to start its monophenol oxidase activity, because of the necessity to reduce Cu2+ to Cu+ because only then the binuclear copper center type 3 of tyrosinase can bind dioxygen to oxidize tyrosine
additional information
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tyrosinase has a di-copper active site, homology modeling using crystal structure PDB ID 3W6W as template. The L-tyrosine-binding residues of tyrosinase active site pocket are highly conserved
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