InterPro domain: IPR002109

Glutaredoxins [ 1 , 2 , 3 ], also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system [ 4 ].

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond [ 5 ]. It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates [ 6 , 7 , 8 , 9 ]. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed [ 10 ] that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

This entry represents Glutaredoxin.

1. Thioredoxin and related proteins in procaryotes. FEMS Microbiol. Rev. 4, 271-97
2. Thioredoxin and glutaredoxin: small multi-functional redox proteins with active-site disulphide bonds. Biochem. Soc. Trans. 16, 95-6
3. Thioredoxin and glutaredoxin systems. J. Biol. Chem. 264, 13963-6
4. Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system. Antioxid. Redox Signal. 6, 63-74
5. The glutaredoxin -C-P-Y-C- motif: influence of peripheral residues. Structure 12, 289-300
6. Reactivity of the human thioltransferase (glutaredoxin) C7S, C25S, C78S, C82S mutant and NMR solution structure of its glutathionyl mixed disulfide intermediate reflect catalytic specificity. Biochemistry 37, 17145-56
7. Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction. J. Mol. Biol. 292, 151-61
8. Catalysis of thiol/disulfide exchange. Glutaredoxin 1 and protein-disulfide isomerase use different mechanisms to enhance oxidase and reductase activities. J. Biol. Chem. 280, 21099-106
9. Glutaredoxin: role in reversible protein s-glutathionylation and regulation of redox signal transduction and protein translocation. Antioxid. Redox Signal. 7, 348-66
10. Vaccinia virus encodes a protein with similarity to glutaredoxins. Virology 181, 378-81