Galactose oxidase cofactor biogenesis

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. 

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. 

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