ChemInform Abstract: Copper-O2 Reactivity of Tyrosinase Models Towards External Monophenolic Substrates: Molecular Mechanism and Comparison with the Enzyme

Institut für Anorganische Chemie, Christian-Albrechts-Universität zu Kiel, Max-Eyth-Straße 2, 24118 Kiel, Germany.
Chemical Society Reviews (Impact Factor: 33.38). 03/2011; 40(7):4077-98. DOI: 10.1039/c0cs00202j
Source: PubMed


The critical review describes the known dicopper systems mediating the aromatic hydroxylation of monophenolic substrates. Such systems are of interest as structural and functional models of the type 3 copper enzyme tyrosinase, which catalyzes the ortho-hydroxylation of tyrosine to DOPA and the subsequent two-electron oxidation to dopaquinone. Small-molecule systems involving μ-η²:η² peroxo, bis-μ-oxo and trans-μ-1,2 peroxo dicopper cores are considered separately. These tyrosinase models are contrasted to copper-dioxygen systems inducing radical reactions, and the different mechanistic pathways are discussed. In addition to considering the stoichiometric conversion of phenolic substrates, the available catalytic systems are described. The second part of the review deals with tyrosinase. After an introduction on the occurrence and function of tyrosinases, several aspects of the chemical reactivity of this class of enzymes are described. The analogies between the small-molecule and the enzymatic system are considered, and the implications for the reaction pathway of tyrosinase are discussed (140 references).

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    • "These highly reactive molecules react further in a non-enzymatic way to form melanin (Rolff et al., 2011). The discrimination between the two catalytic reactions seems to depend on the presence of bivalent ions and of phenolic amino acids covering the access to CuA which inhibits the monophenolase activity (Decker & Rimke, 1998; Rolff et al., 2011). Unlike tyrosinase, laccases exhibit no monophenolase activity but oxidize a wide spectrum of different polyphenols and other compounds by a radical mechanism (Claus & Strong, 2010; Mayer & Staples, 2002). "
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    ABSTRACT: Polyphenoloxidases (PPO) of the type-3 copper protein family are considered to be catecholoxidases catalyzing the oxidation of o-diphenols to their corresponding quinones. PPO from Grenache grapes has recently been reported to display only diphenolase activity. In contrast, we have characterized PPOs from Dornfelder and Riesling grapes which display both monophenolase and diphenolase activity. Ultracentrifugation and size exclusion chromatography indicated that both PPOs occur as monomers with Mr of about 38kDa. Non-reducing SDS-PAGE shows two bands of about 38kDa exhibiting strong activity. Remarkably, three bands up to 60kDa displayed only very weak PPO activity, supporting the hypothesis that the C-terminal domain covers the entrance to the active site. Molecular dynamic analysis indicated that the hydroxyl group of monophenolic substrates can bind to CuA after the flexible but sterically hindering Phe 259 swings away on a picosecond time scale. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Food Chemistry 09/2015; 183. DOI:10.1016/j.foodchem.2015.03.016 · 3.39 Impact Factor
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    • "The weakening of interaction between neighboring FUs of different asymmetric units is likely to greatly decrease the stability of the overall architecture of isomeric HdH1, possibly due to this interaction defect. The loss or decrease in interaction between FUs in isomeric HdH1 may render the movement of βsheet domains of FUs away from their PO core domains easier, which had been showed that PO activation is mostly associated with [1], [35]. This movement can result in greater exposure of the active PO sites, which ultimately contributes to switching the function of HdH1 to predominantly PO enzymatic activity. "
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    ABSTRACT: Hemocyanins (Hcs) of arthropods and mollusks function not only as oxygen transporters, but also as phenoloxidases (POs). In invertebrates, PO is an important component in the innate immune cascade, where it functions as the initiator of melanin synthesis, a pigment involved in encapsulating and killing of pathogenic microbes. Although structures of Hc from several species of invertebrates have been reported, the structural basis for how PO activity is triggered by structural changes of Hc in vivo remains poorly understood. Here, we report a 6.8 Å cryo-electron microscopy (cryo-EM) structure of the isomeric form of hemocyanin, which was isolated from Abalone Shriveling syndrome-associated Virus (AbSV) infected abalone (Halitotis diversicolor), and build a pseudoatomic model of isomeric H. diversicolor hemocyanin 1 (HdH1). Our results show that, compared with native form of HdH1, the architecture of isomeric HdH1 turns into a more relaxed form. The interactions between certain functional units (FUs) present in the native form of Hc either decreased or were totally abolished in the isomeric form of Hc. As a result of that, native state Hc switches to its isomeric form, enabling it to play its role in innate immune responses against invading pathogens.
    PLoS ONE 06/2014; 9(6):e98766. DOI:10.1371/journal.pone.0098766 · 3.23 Impact Factor
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    • "These intermediates have characteristic resonance Raman spectra. Synthetic studies provide models of both complexes and evidence for rapid equilibrium between the two forms [3]. The monophenol hydroxylase and diphenoloxidase activities of tyrosinases are the basis for many industrial biotechnological applications like in environmental technology for the detoxification of phenol-containing waste waters and contaminated soils as a construction of a biosensor for the detaction of phenolic compound [4] and in pharmaceutical industries for the production of o-diphenols (e.g., L-DOPA, dopamine for the treatment of Parkinson's disease) and also have been tested as a marker in melanoma patients [5] and as a target for the activation of prodrugs [6] in food industries for modification of food proteins via crosslinking affects [7]. "
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    ABSTRACT: Tyrosinase is a natural enzyme and is often purified to only a low degree and it is involved in a variety of functions which mainly catalyse the o-hydroxylation of monophenols into their corresponding o-diphenols and the oxidation of o-diphenols to o-quinones using molecular oxygen, which then polymerizes to form brown or black pigments. The synthesis of o-diphenols is a potentially valuable catalytic ability and thus tyrosinase has attracted a lot of attention with respect to industrial applications. In environmental technology it is used for the detoxification of phenol-containing wastewaters and contaminated soils, as biosensors for phenol monitoring, and for the production of L-DOPA in pharmaceutical industries, and is also used in cosmetic and food industries as important catalytic enzyme. Melanin pigment synthesized by tyrosinase has found applications for protection against radiation cation exchangers, drug carriers, antioxidants, antiviral agents, or immunogen. The recombinant V. spinosum tryosinase protein can be used to produce tailor-made melanin and other polyphenolic materials using various phenols and catechols as starting materials. This review compiles the recent data on biochemical and molecular properties of microbial tyrosinases, underlining their importance in the industrial use of these enzymes. After that, their most promising applications in pharmaceutical, food processing, and environmental fields are presented.
    Biochemistry Research International 05/2014; 2014(2):854687. DOI:10.1155/2014/854687
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