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 b ovine TSA. The cDNA clone encoded an open reading frame capable of enc oding a 198-residue polypeptide. The rat and yeast TSA proteins Show s ignificant sequence homology to the 21-kDa component (AhpC) of Salmone lla typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity. AhpC and TSA define a family of >25 differ ent proteins present in organisms from all kingdoms. The similarity am ong the family members extends over the entire sequence and ranges bet ween 23% and 98% identity. A majority of the members of the AhpC/TSA f amily contain two conserved cysteines. At least eight of the genes enc oding AhpC/TSA-like polypeptides are found in proximity to genes encod ing other oxidoreductase activities, and the expression of several Of the homologs has been correlated with pathogenicity. We suggest that t he AhpC/TSA family represents a widely distributed class of antioxidan t enzymes. We also report that a second family of proteins, defined by the 57-kDa component (AhpF) of alkyl hydroperoxide reductase and by t hioredoxin reductase, has expanded to include six additional members,