title: Evolutionary relationships among copper proteins containing coupled binuclear copper sites.
abstract: The amino acid sequences of different copper proteins containing coupled binuclear copper centers are compared. Hemocyanins from arthropods and molluscs and tyrosinases from three different species were found to share a highly homologous region in the C-terminal parts. This region contains three invariant histidines previously identified as ligands to Cu(B) in Panulirus interruptus hemocyanin by X-ray crystallography (Gaykema et al., Nature 309, 23-29 (1984]. In contrast, the ligand environment for the second copper, Cu(A), proved to be quite variable. It is proposed that hemocyanin and tyrosinase have arisen from a common mononuclear copper protein with the typical Cu(B) site. From this ancestral protein two types of binuclear proteins evolved independently into a tyrosinase and an arthropodan hemocyanin type. The amino acid sequence comparison between human ceruloplasmin and Neurospora crassa laccase together with the results from a preliminary X-ray structure analysis of zucchini ascorbate oxidase showed a close relationship in primary and most likely also in tertiary structure in the C-terminal parts of these enzymes. It is suggested that the multicopper oxidases have evolved from an ancestral copper protein which presumably contained all the ligands required for the binding of one binuclear and two additional mononuclear metal centers.
mesh_terms: D000818:Animals; D001204:Ascorbate Oxidase / Q000378:metabolism; D005075:Biological Evolution; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D006433:Hemocyanins / Q000378:metabolism; D006801:Humans; D042845:Laccase; D008667:Metalloproteins / Q000235:genetics* / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism
chemical_list: D008667:Metalloproteins; D003300:Copper; D006433:Hemocyanins; D010088:Oxidoreductases; D042845:Laccase; D001204:Ascorbate Oxidase; D014442:Monophenol Monooxygenase; D002570:Ceruloplasmin