Disease relevance of GRX1

• The results demonstrate a novel hydrogen transport system in E. coli consisting of NADPH, glutathione, glutathione reductase, and a heat-stable enzyme called "glutaredoxin". Reduced glutathione at physiological concentrations functions as hydrogen donor for ribonucleotide reduction only in the presence of glutaredoxin [1].

High impact information on GRX1

• In contrast, depletion of the Hsp70 chaperone Ssq1p, its co-chaperone Jac1p or the glutaredoxin Grx5p markedly increased the amount of Fe/S clusters bound to Isu1p, even though these mitochondrial proteins are crucial for maturation of Fe/S proteins [2].
• In Saccharomyces cerevisiae, two glutaredoxins (Grx1 and Grx2) containing a cysteine pair at the active site had been characterized as protecting yeast cells against oxidative damage [3].
• In this work, another subfamily of yeast glutaredoxins (Grx3, Grx4, and Grx5) that differs from the first in containing a single cysteine residue at the putative active site is described [3].
• Mutants lacking Grx5 are partially deficient in growth in rich and minimal media and also highly sensitive to oxidative damage caused by menadione and hydrogen peroxide [3].
• The interaction between glutaredoxins and Aft1 is not modulated by the iron status of cells but is dependent on the conserved glutaredoxin domain Cys residue [4].

Biological context of GRX1

• Elevating the gene dosage of GRX1 or GRX2 increases resistance to hydroperoxides including hydrogen peroxide, tert-butyl hydroperoxide and cumene hydroperoxide [5].
• Analysis of the Grx1 active site residues shows that Cys-27, but not Cys-30, is required for both the peroxidase and transferase activities, indicating that these reactions proceed via a monothiol mechanism [6].
• In addition, a grx1 mutant was sensitive to oxidative stress induced by the superoxide anion, whereas a strain that lacked GRX2 was sensitive to hydrogen peroxide [7].
• A number of cellular factors have been implicated in the regulation of redox homeostasis, including the glutathione/glutaredoxin and thioredoxin systems [8].
• The ArsC from Escherichia coli plasmid R773 and the eukaryotic ACR2p reductase from Saccharomyces cerevisiae represent two distinct glutaredoxin-linked ArsC classes [9].

Associations of GRX1 with chemical compounds

• The yeast Saccharomyces cerevisiae contains two glutaredoxins, encoded by GRX1 and GRX2, which are active as glutathione-dependent oxidoreductases [5].
• Furthermore, both Grx1 and Grx2 are shown be active as glutathione S-transferases (GSTs), and their activity with model substrates such as 1-chloro-2,4-dinitrobenzene is similar to their activity with hydroperoxides [6].
• Thus, Grx1 and Grx2 function differently in the cell, and we suggest that glutaredoxins may act as one of the primary defenses against mixed disulfides formed following oxidative damage to proteins [7].
• Thus yeast glutaredoxin is unable to substitute for thioredoxin in sulfate assimilation [10].
• However, during oxidation by H(2)O(2), hydroxyethyl disulfide, or cystine, the glutaredoxin domain reacted first, followed by a rate-limiting (0.13 min(-)(1)) transfer of a disulfide bond to the other domain [11].

Regulatory relationships of GRX1

• GRX1 contains a single STRE element and is induced to significantly higher levels compared to GRX2 following heat and osmotic shock [12].

Other interactions of GRX1

• A single glutaredoxin or thioredoxin gene is essential for viability in the yeast Saccharomyces cerevisiae [13].
• We recently reported that Grx1 is active as a glutathione peroxidase and can directly reduce hydroperoxides (Collinson, E. J., Wheeler, G. L., Garrido, E. O., Avery, A. M., Avery, S. V., and Grant, C. M. (2002) J. Biol. Chem. 277, 16712-16717) [6].
• These data suggest that Ure2 possesses a central role in metal ion detoxification, a role not demonstrably shared by either of the two known S. cerevisiae glutathione S-transferases, Gtt1 and Gtt2, or the two glutaredoxins, Grx1 and Grx2, that also possess glutathione S-transferase activity [14].
• This suggests that during the catalytic cycle, Acr2p forms a mixed disulfide with GSH before being reduced by glutaredoxin to regenerate the active Acr2p reductase [15].
• Yeast Grx5 is the only glutaredoxin-like protein studied biochemically so far [16].

Analytical, diagnostic and therapeutic context of GRX1

• Immunoaffinity purified anti-thioredoxin and anti-glutaredoxin antibodies were used to develop competitive indirect ELISA assays that were validated giving very good linearity, reproducibility, sensitivity and parallelism [17].
• The glutaredoxin (Grx) immunoassay is the first quantitative method described to measure the protein [17].
• Crystallization of mutant forms of glutaredoxin Grx1p from yeast [18].

References