Cloning and Sequencing of Thiol-Specific Antioxidant from Mammalian Brain: Alkyl Hydroperoxide Reductase and Thiol-Specific Antioxidant Define a Large Family of Antioxidant Enzymes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 15; pp. 7017 - 7021
• Main Authors: Chae, Ho Zoon, Robison, Keith, Poole, Leslie B., Church, George, Storz, Gisela, Rhee, Sue Goo
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 19.07.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antioxidants; Antioxidants - chemistry; Antioxidants - metabolism; Base Sequence; Biochemistry; Brain; Brain - enzymology; Cattle; Cloning, Molecular; Complementary DNA; Deoxyribonucleic acid; DNA; Enzymes; Family members; Humans; Immunity (Disease); Molecular Sequence Data; Open reading frames; Oxidoreductases - chemistry; Oxidoreductases - metabolism; Peroxidases; Peroxides; Peroxiredoxins; Proteins; Proteins - chemistry; Proteins - metabolism; Rats; Rodents; Sequence Homology, Amino Acid; Sequencing; Ungulates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.15.7017

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.