A THIOL-SPECIFIC ANTIOXIDANT AND SEQUENCE HOMOLOGY TO VARIOUS PROTEINS OF UNKNOWN FUNCTION

Yeast and mammalian cells contain a 25 kDa enzyme that protects cellul ar components against oxidative damage from a system capable of genera ting reactive sulfur species, but not from a system that generates onl y reactive oxygen species. Yeast and rat cDNAs corresponding to this t hiol-specific antioxidant (TSA) have been cloned and sequenced. Rat TS A is 65.3% identical and 76.2% similar to yeast TSA in amino acid sequ ence. A search of the GenBank database revealed 12 additional TSA-like proteins, which show sequence identity to rat TSA ranging from 31 to 76%. Except for the AhpC protein identified in Salmonella typhimurium, none of the TSA-like proteins is associated with known cellular funct ions. AhpC, which exhibits similar to 40% sequence identity to TSA, ha s been proposed to be a catalytic component of alkyl hydroperoxide red uctase. Alignment of rat and yeast TSA with the TSA-like sequences rev ealed two conserved cysteine residues, one conserved in all 14 sequenc es and the other in 12 sequences. The most conserved cysteine is locat ed in a well-conserved motif of (hydrophobic ue-Asp-Phe-Thr-Phe-Val-Cy s-Pro-Thr-Glu-hydrophobic residue. These results suggest that the TSA- like proteins of previously unknown function may represent a widely di stributed family of antioxidants with functions similar to those of TS A and AhpC.