This enzyme catalyzes the two distinct reactions as follows: (1) L-tyrosine + 1/2 O2 = L-dopa (ortho hydroxylation of monophenol; monophenolase activity) (2) L-dopa + 1/2 O2 = dopaquinone + H2O (two-electron oxidation of ortho-diphenol; diphenolase activity) This enzyme belongs to the type-3 copper protein family, which includes hemocyanin and catechol oxidase (EC 1.10.3.1). The type-3 copper proteins contain a binuclear copper active site, which consists of two closely spaced copper atoms each coordinated by three histidine residues (see [10], [12], [14]). Catechol oxidase can catalyze only oxydation of ortho-diphenol, but lacks hydroxylation activity for monophenol. According to the literature, the dinuclear copper active site exists in three redox forms: (a) The deoxy (reduced) form [Cu(I)-Cu(I)]; (b) The oxy (oxidized) form [Cu(II)-O2(2-)-Cu(II)]; Molecular oxygen is bound as peroxide in a side-on bridging mode. (c) The met (resting) form [Cu(II)-OH(-)-Cu(II)]; Cu(II) ions are bridged to either a water molecule or hydroxide ion. The deoxy form can bind a molecular oxygen to give the oxy form. Moreover, there is another redox form, half-met form [Cu(I)-OH(-)-Cu(II)], which is EPR active (see [12]). In this form, one of the two coppers is in the oxidized form. According to the literature [15] and [22], the met form can be categorized into two types: met I with a single bridging ligand, and met II with two bridging ones. Here, CuA is coordinated by His42, His60 and His69 (of 3nm8 in PDB), whereas CuB is coordinated by His His204, His208 and His231. There has been long-standing debate on whether substrate hydroxyl groups bind to CuA or CuB, particluarly for monophenolase reaction. The literature ([15], [20], [22] and [25]) supports the mechanism in which monophenol hydroxyl group is bound to CuA, whereas other reports ([12], [14] and [23]) suggest that monophenol docks to CuB.
di-copper center containing domain from catechol oxidase
Monophenol dihydroxyphenylalanine:oxygen oxidoreductase
Monophenol, dihydroxy-L-phenylalanine oxygen oxidoreductase
HIS 42;HIS 60;HIS 69(Copper-1 binding);HIS 204;HIS 208;HIS 231(Copper-2 binding)
HIS 38;HIS 54;HIS 63(Copper-1 binding);HIS 190;HIS 194;HIS 216(Copper-2 binding)
The first crystal structure of tyrosinase: all questions answered?
Investigation of Streptomyces antibioticus tyrosinase reactivity toward chlorophenols.
Changes in tyrosinase specificity by ionic liquids and sodium dodecyl sulfate.
Protein and active-site structure of tyrosinase.
Identification of two histidines as copper ligands in Streptomyces glaucescens tyrosinase.
Stabilization of the oxy form of tyrosinase by a single conservative amino acid substitution.
Tyrosinase: a comprehensive review of its mechanism.
Roles of copper ligands in the activation and secretion of Streptomyces tyrosinase.
1H NMR spectroscopy of the binuclear Cu(II) active site of Streptomyces antibioticus tyrosinase.
EPR study of the dinuclear active copper site of tyrosinase from Streptomyces antibioticus.
Tyrosinase-catalyzed oxidation of fluorophenols.
Structural basis and mechanism of the inhibition of the type-3 copper protein tyrosinase from Streptomyces antibioticus by halide ions.
Molecular anatomy of tyrosinase and its related proteins: beyond the histidine-bound metal catalytic center.
Spectroscopic characterization of the electronic changes in the active site of Streptomyces antibioticus tyrosinase upon binding of transition state analogue inhibitors.
Interaction between the type-3 copper protein tyrosinase and the substrate analogue p-nitrophenol studied by NMR.
Paramagnetic properties of the halide-bound derivatives of oxidised tyrosinase investigated by 1H NMR spectroscopy.
X-RAY CRYSTALLOGRAPHY (1.20 ANGSTROMS) IN COMPLEX WITH COPPER.
Crystallographic evidence that the dinuclear copper center of tyrosinase is flexible during catalysis.
A tyrosinase with an abnormally high tyrosine hydroxylase/dopa oxidase ratio.
X-ray absorption analysis of the active site of Streptomyces antibioticus Tyrosinase upon binding of transition state analogue inhibitors.
Modeling tyrosinase activity. Effect of ligand topology on aromatic ring hydroxylation: an overview.
Isolation, cloning and characterization of a tyrosinase with improved activity in organic solvents from Bacillus megaterium.
New insights into the active site structure and catalytic mechanism of tyrosinase and its related proteins.
Acta Crystallogr Sect F Struct Biol Cryst Commun
Crystallization and preliminary X-ray crystallographic analysis of a bacterial tyrosinase from Bacillus megaterium.
Structural and mechanistic insights into the oxy form of tyrosinase from molecular dynamics simulations.
A molecular mechanism for copper transportation to tyrosinase that is assisted by a metallochaperone, caddie protein.
X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH COPPER AND ZINC.
First structures of an active bacterial tyrosinase reveal copper plasticity.
Influencing the monophenolase/diphenolase activity ratio in tyrosinase.