Ceruloplasmin has a distinct active site for the catalyzing glutathione-dependent reduction of alkyl hydroperoxide.
Ceruloplasmin, a blue multi-copper alpha(2)-glycoprotein found in the plasma of all vertebrates, is capable of oxidizing aromatic amines and ferrous iron. Here, we report that human ceruloplasmin exhibits an alkyl hydroperoxide peroxidase activity, which is independent of the oxidase activity. The site-specific modification of the sulfhydryl of cysteine at position 699 in ceruloplasmin completely abolished the antioxidant activity, suggesting that ceruloplasmin is a peroxidase with a cysteinyl thiol as a functional nucleophile. The crystal structure of human ceruloplasmin reveals that the domain containing Cys-699 is apart from the multi-copper complex domains. Taken together, these data suggest that ceruloplasmin has a distinct active site for a glutathione-linked peroxidase activity apart from the copper complex site exerting ferroxidase activity.
Cha
M K
MK
National Creative Research Initiative Center for Antioxidant Proteins, Department of Biochemistry, Pai-Chai University, Taejon, Korea.
Kim
I H
IH
D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D002570:Ceruloplasmin / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D010544:Peroxidases; D054464:Peroxiredoxins; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000975:Antioxidants; D010446:Peptide Fragments; D011506:Proteins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; D002570:Ceruloplasmin; D005978:Glutathione; D003545:Cysteine