Amine oxidases Galactose oxidase

The simple coordination chemistry characteristic of the majority of protein-metal interactions is replaced in certain cases by irreversible covalent modifications of the protein mediated by the metal ion. These modifications are essential for the function and are templated by the structure of the protein, as no other proteins are required for the reaction to occur. These self-processing reactions result in the biogenesis of redox cofactors in some enzymes (amine oxidases, galactose oxidase, cytochrome c oxidase) and activation of hydrolytic sites in others (nitrile hydratase). The active sites of all of these enzymes are bifunctional, directing not only the catalytic turnover reaction of the mature enzyme but the modification steps required for maturation. 

Nonblue oxidases Amine oxidase Diamine oxidases Galactose oxidase Cytochrome c oxidase... 

The function of the metal site in the oxygen-dependent radical enzymes galactose oxidase, amine oxidases, ribonucleotide reductase, and cytochrome c oxidase is inter alia to bind 02 in their reduced forms and undergo the appropriate redox chemistry to generate a metal-bound, activated oxygen species of variable nature. 

So-called blue multinuclear copper oxidase enzymes, such as laccase and ascorbate oxidase, catalyze the stepwise oxidation of organic substrates (most likely in successive one-electron steps) in tandem with the four-electron reduction of O2 to water, i.e. no oxygen atom(s) from O2 are incorporated into the substrate (Eq. 4) [15]. Catechol oxidase, containing a type 3 center, mediates a two-electron substrate oxidation (o-diphenols to o-chinones), and turnover of two substrate molecules is coupled to the reduction of O2 to water [34,35]. The non-blue copper oxidases, e.g. galactose oxidase and amine oxidases [27,56-59], perform similar oxidation catalysis at a mononuclear type 2 Cu site, but H2O2 is produced from O2 instead of H2O, in a two-electron reduction. 

Galactose oxidase (pdb 1GOF) Amine oxidase (pdb ID6Z)... 

The paramagnetic copper present in the non-blue oxidases such as galactose oxidase and amine oxidases, and also in the blue oxidases, has d-d and ESR spectra typical of coordination complexes of copper(II). 

Nonblue. These include galactose oxidase (GO) and amine oxidases (e.g., plasma amine oxidase, diamine oxidase, lysyl oxidase), which produce dihydrogen peroxide by the two-electron reduction of 02 [33], For GO (stereospecific primary alcohol oxidation), spectroscopic studies by Whittaker [70,71] suggest that the two-electron oxidation carried out by a mononuclear copper center is aided by a stabilized ligand-protein radical (i.e., (L)Cu(I) + 02 —> (L +)Cu(lI) + H202), obviating the need to get to Cu(III) in the catalytic cycle. Protein x-ray structures [33,72] reveal a novel copper protein cofactor, which would seem... 

Oxidation galactose oxidase, amine oxidase, ascorbate oxidase, laccase, cytochrome c oxidase... 

Fig. 9. Redox-active amino acid residues related to tyrosine, (a) Tyrosine, the redox center in ribonucleotide reductase, prostaglandin H synthase, and the photosynthetic oxygen evolving complex, (b) 2,4,5-Trihydroxyphenylalanine, the redox cofactor of the quinoprotein amine oxidase, (c) Tyrosine-cysteine (Tyr-Cys), the redox cofactor of galactose oxidase.

Product of SOD and non-blue oxidases (galactose and amine oxidases)... 

Over the past 10 years, our understanding of enzymes which effect the difficult chemical process of C6H bond cleavage has increased dramatically (Stubbe, 1989 Klinman, 1996). We know that nature employs both metal ions and reactive organic cofactors, such as radicals and quinones, derived by post-translational modification of aminoacids in the polypeptide chain of the enzyme. The two enzymes to be described in the present review are good examples galactose oxidase employs copper and a tyrosine covalently cross-linked to a cysteine to stabilize a radical whilst amine oxidases employ copper and tyrosine-derived quinones. There is subtle interplay between the roles played by copper in the biogenesis of these novel cofactors and in the catalytic cycle of the oxidases. 

In this review, current understanding of the structure and function of galactose oxidase and amine oxidases will be described together with comparisons between them and future directions in this field. 

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