Structure and function of copper-containing proteins

Insight gained from three-dimensional structures of several cupredoxins has led to site-directed mutagenesis of copper ligands and of adjacent residues relevant to the electron-transfer function of these molecules. Results from these studies have shown that the methionine ligand can be modified and will not perturb function greatly, whereas a conserved hydrophobic patch is important to function. A new X-ray structure of nitrite reductase shows that it is a trimer with unexpected sequence and structural similarity to ascorbate oxidase, another multicopper protein of known structure. Each of these multicopper proteins has domain folds like that of the cupredoxins (and superoxide dismutase). The structure of galactose oxidase reveals a three-domain structure which includes one domain with a fold related to the cupredoxin fold, and one with a fold related to that of methylamine dehydrogenase. This structural study also reveals a novel covalent linkage of a cysteine to a tyrosine ligand of the copper center. This linked pair is believed to be the source of a tyrosine radical important to the function of the molecule.