Disease relevance of grxA

• The disulfide bonds in these latter enzymes are reduced in Escherichia coli by two systems; the thioredoxin pathway and the glutathione/glutaredoxin pathway [1].
• Identification of a second functional glutaredoxin encoded by the bacteriophage T4 genome [2].
• The same relationship has been proposed for the glutaredoxin and R1 proteins expressed by all orthopoxviruses, including vaccinia, variola, and ectromelia virus [3].
• To study structure-function relationships of the vertebrate Grx-1 family, and reveal potential viral adaptations, we have determined crystal structures of the ectromelia virus glutaredoxin, EVM053, in the oxidized and reduced states [3].
• The torsion angle around the S-S bond is smaller than that normally observed for disulfides: 58 degrees, 67 degrees and 67 degrees for wild-type glutaredoxin molecule A and B and mutant glutaredoxin, respectively [4].

High impact information on grxA

• The gene encoding Grx1 is regulated by OxyR, thus providing a mechanism for autoregulation [5].
• The amino acid sequence of glutaredoxin has been aligned to those of the thioredoxins assuming that glutaredoxin has the same common fold [6].
• A strain of Escherichia coli missing three members of the thioredoxin superfamily, thioredoxins 1 and 2 and glutaredoxin 1, is unable to grow, a phenotype presumed to be due to the inability of cells to reduce the essential enzyme ribonucleotide reductase [7].
• To study this, the Escherichia coli glutaredoxin gene (255 base pairs) was inactivated by inserting a 2-kilobase kanamycin-resistance fragment into the coding sequence of the cloned gene [8].
• Further experiments with molecular genetic techniques are required to define the relative roles of the thioredoxin and glutaredoxin systems in intracellular redox reactions [9].

Chemical compound and disease context of grxA

• In Escherichia coli ArsC catalyzes the reduction of arsenate to arsenite using GSH with glutaredoxin as electron donors [10].
• Functional analysis of the Escherichia coli genome using the sequence-to-structure-to-function paradigm: identification of proteins exhibiting the glutaredoxin/thioredoxin disulfide oxidoreductase activity [11].
• In this mutant glutaredoxin, the active site residues Val15 and Tyr16 have been substituted by Gly and Pro, respectively, to mimic that of Escherichia coli thioredoxin [4].
• EVM053 also exhibits a novel cis-proline (Pro53) in a loop that has been shown to contribute to R1-binding in Escherichia coli Grx-1 [3].
• By selectively mutating the two cysteines in the peptide, we have identified the electrophilic cysteine as C759 (B1 numbering) and prepared a mixed disulfide between E. coli glutaredoxin-1 (C14 --> S) and the C759 monothiol form of the peptide [12].

Biological context of grxA

• Thus, despite an identical active site disulfide motif and a similar secondary structure and tertiary fold, Grx3 and Grx1 display large functional differences in in vitro protein disulfide oxido-reduction reactions [13].
• Glutaredoxin protects cerebellar granule neurons from dopamine-induced apoptosis by dual activation of the ras-phosphoinositide 3-kinase and jun n-terminal kinase pathways [14].
• What we have learned about nrdHIEF expression indicates strong differences between its regulation and that of the nrdAB operon and of genes coding for components of both thioredoxin/glutaredoxin pathways [15].
• We examined the in vivo expression of up to 16 genes encoding for components of both glutaredoxin and thioredoxin systems and for members of the OxyR and SoxRS regulons [16].
• Significant up-regulation of catalase activity was observed in null mutants for thioredoxin 1 and the three glutaredoxins, whereas up-regulation of glutaredoxin activity was observed in catalase-deficient strains with additional defects in the thioredoxin pathway [17].

Anatomical context of grxA

• A role of the glutaredoxin mechanism in the endoplasmic reticulum is suggested [18].

Associations of grxA with chemical compounds

• Affinity chromatography was used to bind glutaredoxin on a glutathione-containing thiol-Sepharose column [19].
• We conclude that Grx acts by reducing mixed disulfides between GSH and RNase that are rate-limiting in enzyme-catalyzed refolding [20].
• A mutant Grx in which one of the active site cysteine residues (Cys-11 and Cys-14) had been replaced by serine, C14S Grx, had similar effect compared with its wild-type counterpart [20].
• The activities of the mutant proteins were determined in the presence of three different reductants: thioredoxin, glutaredoxin, or dithiothreitol [21].
• Purified Y55.7 protein had glutathione-dependent thioltransferase and dehydroascorbate reductase activities indicative of a functional glutaredoxin [2].

Other interactions of grxA

• The redox protein from PH0178 had strong thioredoxin-like activity, but no glutaredoxin activity [22].

Analytical, diagnostic and therapeutic context of grxA

• A gene replacement technique was used to obtain a strain, A407, that lacked glutaredoxin by radioimmunoassay and by enzymatic assay with ribonucleotide reductase [8].
• Highly sensitive and specific enzyme-linked immunoassays were developed to confirm that trx-grx- cells lacked thioredoxin and glutaredoxin [23].
• By using site-directed mutagenesis techniques, the essential amino acids at the catalytic center of porcine thioltransferase (glutaredoxin) were determined [24].
• We have demonstrated that a 25-residue peptide corresponding to this C-terminal sequence is a very good substrate for glutaredoxin via a fluorescence assay and that this peptide binds in a specific manner via isothermal titration calorimetric measurements [12].
• Some aspects of Mj0307's unique behavior can be explained by comparing structure-based sequence alignments with mesophilic bacterial and eukaryotic glutaredoxin and thioredoxin proteins [25].

References