| Description | Glutaredoxins [ , , ], 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 [].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 [ ]. 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 [ , , , ]. 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 [ ] 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.Unlike other glutaredoxins, glutaredoxin 2 (Grx2) cannot reduce ribonucleotide reductase [ ]. Grx2 has significantly higher catalytic activity in the reduction of mixed disulphides with glutathione (GSH) compared with other glutaredoxins. It adopts a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal α helical domain. The active site residues (Cys9-Pro10-Tyr11-Cys12, in Escherichia coli Grx2, ), which are found at the interface between the N- and C-terminal domains are identical to other glutaredoxins, but there is no other similarity between glutaredoxin 2 and other glutaredoxins. Grx2 is structurally similar to glutathione-S-transferases (GST), but there is no obvious sequence similarity [ ]. The inter-domain contacts are mainly hydrophobic, suggesting that the two domains are unlikely to be stable on their own. Both domains are needed for correct folding and activity of Grx2. It is thought that the primary function of Grx2 is to catalyse reversible glutathionylation of proteins with GSH in cellular redox regulation including the response to oxidative stress. The N-terminal domain is . | Name | Glutaredoxin 2, C-terminal |
| Short Name | Glutaredoxin2_C | Type | Domain |
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