Self-assembly of the oxy-tyrosinase core and the fundamental components of phenolic hydroxylation
Self-assembly of the oxy-tyrosinase core and the fundamental components of phenolic hydroxylation
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DOI：
10.1038/nchem.1284
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发表时间：
2012-04-01
期刊：
影响因子：
21.8
通讯作者：
Stack, T. Daniel P.
中科院分区：
文献类型：
--
作者：
Citek, Cooper;Lyons, Christopher T.;Stack, T. Daniel P.
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 mu-eta(2):eta(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 degrees 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 Cu2O2 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.
