Although fewer in number, copper enzymes are an alternative to iron enzymes in many biosynthetic pathways. All the functions associated with iron enzymes can be found in copper enzymes: electron transfer, oxygen transport and storage, oxygenation and oxidation. Among these, the mono-oxygenases are of particular interest as they are involved in important biological processes in mammals. Tyrosinase (Ty) is involved in melanin biosynthesis. Its dysfunction is implicated in metastatic melanoma. Dopamine beta-hydroxylase (DBH) and peptidylglycine alpha-amidating hydroxylase (PHM) catalyze the key steps in the biosynthesis of the neurotransmitters noradrenaline (DBH) and amidated neuropeptides (oxytocin, neuropeptide Y, etc.) (PHM). To complete the picture, mono-oxygenases are also found in methanotrophic bacteria, where they oxidize methane to methanol (membrane methane mono-oxygenase, pMMO), and in fungi (GH61), where they catalyze cellulose oxidation.
To activate oxygen and make it reactive, several " strategies " are deployed by nature, strategy:(i) with two closely linked coppers(dCuCu≈ 3.6 Å) involving peroxidic entities of type μ - η2:η2 for tyrosinase;(ii) two distantly related coppers(dCuCu > 11 Å) involving hydroperoxide and/or superoxide entities for DBH, PHM and pMMO, and(iii) a single copper for GH61. These various points were discussed during the seminar and placed in a more general context of oxygen activation. We were particularly interested in the reactivity of the different copper-associated reduced oxygen species in enzymes and their models.
