title: Self-assembly of the oxy-tyrosinase core and the fundamental components of phenolic hydroxylation.
abstract: The enzyme tyrosinase contains two Cu(I) centres, trigonally coordinated by imidazole nitrogens of six conserved histidine residues. The enzyme activates O(2) to form a µ-η(2):η(2)-peroxo-dicopper(II) core, which hydroxylates tyrosine to a catechol in the first committed step of melanin biosynthesis. Here, we report a family of synthetic peroxo complexes, with spectroscopic and chemical features consistent with those of oxygenated tyrosinase, formed through the self-assembly of monodentate imidazole ligands, Cu(I) and O(2) at -125 °C. An extensively studied complex reproduces the enzymatic electrophilic oxidation of exogenous phenolic substrates to catechols in good stoichiometric yields. The self-assembly and subsequent reactivity support the intrinsic stability of the Cu(2)O(2) core with imidazole ligation, in the absence of a polypeptide framework, and the innate capacity to effect hydroxylation of phenolic substrates. These observations suggest that a foundational role of the protein matrix is to facilitate expression of properties native to the core by bearing the entropic costs of assembly and precluding undesired oxidative degradation pathways.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California         94305, USA.
authors.forename: Cooper
authors.initials: C
authors.lastname: Citek
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Lyons
authors.forename: Erik C
authors.initials: EC
authors.lastname: Wasinger
authors.forename: T Daniel P
authors.initials: TD
authors.lastname: Stack
mesh_terms: D020134:Catalytic Domain; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry*; D043844:Crown Ethers / Q000737:chemistry; D062385:Hydroxybenzoates / Q000737:chemistry*; D006900:Hydroxylation; D007093:Imidazoles / Q000737:chemistry; D007700:Kinetics; D014442:Monophenol Monooxygenase / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D056831:Coordination Complexes; D043844:Crown Ethers; D062385:Hydroxybenzoates; D007093:Imidazoles; C042148:15-crown-5; D003300:Copper; C029899:imidazole; D014442:Monophenol Monooxygenase; C017616:phenolic acid; D010100:Oxygen