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...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1994-07, Vol.91 (15), p.7017-7021
Hauptverfasser: Chae, Ho Zoon, Robison, Keith, Poole, Leslie B., Church, George, Storz, Gisela, Rhee, Sue Goo
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container_end_page 7021
container_issue 15
container_start_page 7017
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 91
creator Chae, Ho Zoon
Robison, Keith
Poole, Leslie B.
Church, George
Storz, Gisela
Rhee, Sue Goo
description 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.
doi_str_mv 10.1073/pnas.91.15.7017
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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 &gt;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. 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subjects Amino Acid Sequence
Amino acids
Animals
ANTIOXIDANTS
Antioxidants - chemistry
Antioxidants - metabolism
Base Sequence
Biochemistry
BIOLOGY AND MEDICINE, BASIC STUDIES
Brain
Brain - enzymology
Cattle
Cloning, Molecular
Complementary DNA
Deoxyribonucleic acid
DNA
DNA SEQUENCING
DNA-CLONING
Enzymes
Family members
GENES
Humans
Immunity (Disease)
Molecular Sequence Data
Open reading frames
OXIDOREDUCTASES
Oxidoreductases - chemistry
Oxidoreductases - metabolism
Peroxidases
Peroxides
Peroxiredoxins
Proteins
Proteins - chemistry
Proteins - metabolism
Rats
Rodents
Sequence Homology, Amino Acid
Sequencing
Ungulates
title Cloning and Sequencing of Thiol-Specific Antioxidant from Mammalian Brain: Alkyl Hydroperoxide Reductase and Thiol-Specific Antioxidant Define a Large Family of Antioxidant Enzymes
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