Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes.
A cDNA corresponding to a thiol-specific antioxidant enzyme (TSA) was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA. The cDNA clone encoded an open reading frame capable of encoding a 198-residue polypeptide. The rat and yeast TSA proteins show significant sequence homology to the 21-kDa component (AhpC) of Salmonella typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity. AhpC and TSA define a family of > 25 different proteins present in organisms from all kingdoms. The similarity among the family members extends over the entire sequence and ranges between 23% and 98% identity. A majority of the members of the AhpC/TSA family contain two conserved cysteines. At least eight of the genes encoding AhpC/TSA-like polypeptides are found in proximity to genes encoding other oxidoreductase activities, and the expression of several of the homologs has been correlated with pathogenicity. We suggest that the AhpC/TSA family represents a widely distributed class of antioxidant enzymes. We also report that a second family of proteins, defined by the 57-kDa component (AhpF) of alkyl hydroperoxide reductase and by thioredoxin reductase, has expanded to include six additional members.
Chae
H Z
HZ
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Robison
K
K
Poole
L B
LB
Church
G
G
Storz
G
G
Rhee
S G
SG
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D010544:Peroxidases; D054464:Peroxiredoxins; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid
D000975:Antioxidants; D011506:Proteins; D004247:DNA; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins