Table 1.
Deglutathionylation Activities and Glutathionyl Specificity of Glutaredoxins from Prototype Organisms
| Glutaredoxin | CXXbC/S motif | Deglutathionylation activity? | Glutathionyl specificity?a | References |
|---|---|---|---|---|
| Escherichia coli | ||||
| Grx1 | CPYC | Yes (peptide-SSG,ArsC-SSG) | Yes (Step 1) | (14, 53, 96, 117) |
| Grx2 | CPYC | Yes (βME-SSG) | Yes (Step 1) | (4, 135) |
| Grx3 | CPYC | Yes (βME-SSG) | Yes (Step 1) | (4) |
| Grx4 | CGFS | No | N/A | (32) |
| Streptomyces cerevisiae | ||||
| Grx1 | CPYC | Yes (βME-SSG) | ND | (24, 39, 72) |
| Grx2 | CPYC | Yes (βME-SSG,20S proteasome-SSG) | ND | (24, 72, 118) |
| Grx3 | CGFS | Yesb | ND | (105) |
| Grx4 | CGFS | Yesb | ND | (105) |
| Grx5 | CGFS | Unresolvedc | ND | (105, 106, 116, 133) |
| Grx6 | CSYS | Yes | Yes (Step 1) | (79) |
| Grx7 | CPYS | Yes | Yes (Step 1) | (79) |
| Homo sapiens | ||||
| Grx1 | CPYC | Yes (protein-SSG,cysteine-SSG, βME-SSG) | Yes (Steps 1 and 2) | (47, 61, 122, 143) |
| Grx2 | CSYC | Yes (protein-SSG,cysteine-SSG, βME-SSG) | Yes (Steps 1 and 2) | (38, 61) |
| Grx5 | CGFS | ND | ND | (16, 85) |
| Grx domains | ||||
| TGR | CPHS | Yes (βME-SSG) | Yesd | (129, 130) |
| PICOT | CGFS | ND | ND | (57, 142) |
| TR3 | CTRC | No | N/A | (126) |
Indicated by the step of the deglutathionylation reaction for which glutathionyl specificity has been demonstrated (see Fig. 3). Step 1 indicates selectivity for glutathionyl mixed-disulfide substrates and/or for selective attack of Grx on the sulfur of the glutathionyl moiety. Step 2 indicates selectivity for GSH as the second substrate to reduce the Grx-SSG intermediate.
Inferred from studies of null and multicopy mutant strains.
Studies of null mutant strains suggest a contribution to cellular deglutathionylation activity, but assays on purified, recombinant protein show little to no activity.
Activity toward HEDS was GSH dependent (130), but it was not distinguished whether this dependence reflected a requirement for forming a glutathionyl mixed-disulfide first substrate (βME-SSG) from the pro-substrate (HEDS), for using GSH as the preferred second substrate, or both.
ND, not determined. N/A, not applicable.