Copper monooxygenase

Prigge, S. T., Mains, R. E., Eipper, B. A. and Amzel, L. M. New insights into copper monooxygenases and peptide amidation structure, mechanism and function. Cell Mol. Life Sci. 57 1236-1259, 2000. 

Tyrosinase is a monooxygenase which catalyzes the incorporation of one oxygen atom from dioxygen into phenols and further oxidizes the catechols formed to o-quinones (oxidase action). A comparison of spectral (EPR, electronic absorption, CD, and resonance Raman) properties of oxy-tyrosinase and its derivatives with those of oxy-Hc establishes a close similarity of the active site structures in these proteins (26-29). Thus, it seems likely that there is a close relationship between the binding of dioxygen and the ability to "activate" it for reaction and incoiporation into organic substrates. Other important copper monooxygenases which are however of lesser relevance to the model studies discussed below include dopamine p-hydroxylase (16,30) and a recently described copper-dependent phenylalanine hydroxylase (31). 

Transition metal hydroperoxo species are well established as important intermediates in the oxidation of hydrocarbons (8,70,71). As they relate to the active oxygenating reagent in cytochrome P-450 monooxygenase, (porphyrin)M-OOR complexes have come under recent scmtiny because of their importance in the process of (poiphyrin)M=0 formation via 0-0 cleavage processes (72-74). In copper biochemistry, a hydroperoxo copper species has been hypothesized as an important intermediate in the catalytic reaction of the copper monooxygenase, dopamine P-hydroxylase (75,76). A Cu-OOH moiety has also been proposed to be involved in the disproportionation of superoxide mediated by the copper-zinc superoxide dismutase (77-78). Thus, model Cun-OOR complexes may be of... 

As suggested above, we can speculate that the biological relevance of the observations described above pertain to the activation of dioxygen in copper monooxygenases via protonation of a peroxo-Cun (derived from Cu(I) and O2)... 

Mimicking and understanding tyrosinase activity (o-hydroxylation of phenols) have been of longtime interest because this was one of the earliest copper monooxygenases described and the significance of elucidating dioxygen activation mechanism(s) has widespread implications and potential applications. 

III.B.1. A Xylyl-Containing Copper Monooxygenase Model System... 

Turning to the complexes of copper(II), copper(IV) is not stable and heterolysis of the 0—0 bond of the peroxide to form the copper(IV) oxo complex does not occur. In addition, the Lewis acidity of the copper(II) ion is not high enough to enhance the electrophilicity of the coordinated alkyl- or acylperoxide to promote direct oxo-incorporating reactions. With these points in mind, the inert activity of alkyl- and acylperoxo copper(II) complexes, experimentally observed, is understandable, and it is quite unlikely that the mechanism of copper monooxygenase parallels that of cytochrome P-450. 

A Functional Model for Copper Monooxygenases and the NIH Shift Mechanism... 

Figure 4. A copper monooxygenase model system, involving the dicopper-mediated hydroxylation of an arene.

K. Lerch, Copper Monooxygenases Tyrosinase and Dopamine )3-Monooxygenase (R), Metal Ions Biol. Syst. 13 (1981), 143-186. 

N. J. Biackburn, Chemicai and Spectroscopic Studies on Dopamine B-Hydroxyiase and Other Copper Monooxygenases, in Bioinorganic Chemistry of Copper,K. D. Kariin, Z. Tyekiar, Eds. Chapman Haii New York, 1993 pp 164-183. 

Lerch, K. Copper monooxygenases, tyrosinases and dopamine-monooxygenase, in Metal Ions in Biological Systems. Copper Proteins, Siegel, H., Ed., Dekker, New York, 1981, p. 143. 

We have been interested in the noncoupled copper-monooxygenases comprising Peptidylglycine a-Monooxygenase (PHM), Dopamine p-Monooxygenase (DpM), and Tyramine p-Monooxygenase (TpM) that catalyze the hydroxylation of C-H... 

Tyrosinase is a dinuclear copper monooxygenase which catalyzes the ortho-hydvo y X on of phenols to catechols (scheme 10). ... 

Tyrosinase (E.C. 1.14.18.1, monophenol monooxygenase) is a copper monooxygenases enzyme that catalyzes two different oxygen-dependent reactions, namely the oxidations of both monophenols (cresolase or monophenolase activity) and o-diphenols (catecholase or diphenolase activity) into reactive o-quinones [28, 89]. 

Synthetic copper complexes which can activate dioxygen and hydroxylate aliphatic C-H bonds are of great importance, both for shedding light on common industrial processes which employ copper catalysts and also as models for the copper monooxygenases mentioned above, such as OPM, PAM, and pMMO. 

Recent remarkable progress in the clarification of the mechanisms of nonheme iron and copper monooxygenases depends on the X-ray crystallographic and other spectroscopic... 

CHEMICAL MODELS FOR NONHEME IRON AND COPPER MONOOXYGENASES -... 

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