Disease relevance of trxA

• We have overexpressed the anaerobic thioredoxin genes in E. coli to produce functionally active recombinant proteins [1].
• Thioredoxin system in obligate anaerobe Desulfovibrio desulfuricans: Identification and characterization of a novel thioredoxin 2 [1].
• The Anabaena strain 7120 thioredoxin gene did not complement the trxA mutation in E. coli [2].
• The Gram-positive bacterium Streptomyces coelicolor contains three thioredoxins that are involved in unknown biological processes. trxA from S. coelicolor was cloned and expressed in Escherichia coli and the protein purified and crystallized using the hanging-drop method of vapour diffusion [3].
• Bacteriophage T7 DNA polymerase (gene 5 protein, gp5) interacts with its processivity factor, Escherichia coli thioredoxin, via a unique loop at the tip of the thumb subdomain [4].

High impact information on trxA

• Each of these regions contains the presumed active site sequence Trp-Cys-Gly-His-Cys-Lys, suggesting that PDI, similar in action to thioredoxin, catalyses disulphide bond interchange via an internal disulphide-sulphydryl interchange [5].
• DsbD, in turn, is reduced by cytoplasmic thioredoxin, indicating that DsbD transfers disulfidereducing potential from the cytoplasm to the periplasm [6].
• Complementation of DsbA deficiency with secreted thioredoxin variants reveals the crucial role of an efficient dithiol oxidant for catalyzed protein folding in the bacterial periplasm [7].
• The results indicate that thionein (T), which is formed when the zinc is removed from Zn-MT, can function as a reducing system for the Msr proteins because of its high content of cysteine residues and that Trx can reduce oxidized T [8].
• A heat-stable protein has been detected in bovine liver that, in the presence of EDTA, can support the Msr reaction in the absence of either Trx or DTT [8].

Chemical compound and disease context of trxA

• The redox protein and thioredoxin reductase retained their full activities for over 1h at 100 degrees C. The redox potential of the redox protein was similar to that of thioredoxin from E. coli and lower than that of glutathione [9].
• The HeLa enzyme has low species and substrate specificity and can reduce HeLa PI and PIII, E. coli thioredoxin and glutaredoxin, and the disulfide bond in 5,5'-dithiobis(2-nitrobenzoic acid) [10].
• Around the nucleophile cysteine of the active site (-W-C-G-P-C-), chloroplast thioredoxin-f shows lower density of negative charges than the inefficient modulator Escherichia coli thioredoxin [11].
• The reduction rate of Escherichia coli thioredoxin by dithiothreitol is directly proportional to the fraction of Asp-26 in the protonated form over the pH range of 6-9 [12].
• The Thioredoxin Domain of Neisseria gonorrhoeae PilB Can Use Electrons from DsbD to Reduce Downstream Methionine Sulfoxide Reductases [13].

Biological context of trxA

• Plasmids containing gshB were able to complement the glutathione requirement of a trxA gshB double mutant, and cells containing the plasmids were found to have elevated levels of glutathione synthetase [14].
• The comparative analysis of the predicted amino acid sequence of trxA showed that the 11.2 kDa protein (102 aa) shared 26-68% sequence similarity with products of other known trxA genes and contained the conserved active site Cys-Gly-Pro-Cys [15].
• We have developed a versatile Escherichia coli expression system based on the use of E. coli thioredoxin (trxA) as a gene fusion partner [16].
• The complete nucleotide sequence of the trxA gene and its promoter was determined [17].
• We have identified a total of 80 proteins associated with thioredoxin, implicating the involvement of thioredoxin in at least 26 distinct cellular processes that include transcription regulation, cell division, energy transduction, and several biosynthetic pathways [18].

Anatomical context of trxA

• Collectively, our results demonstrate that systemically applied Trx is taken up by the myocardium to exert potent cardioprotective effects in vivo, offering interesting therapeutic avenues [19].
• Here we show that thioredoxin is actively secreted by a variety of normal and transformed cells, including fibroblasts, airway epithelial cells, and activated B and T lymphocytes [20].
• Upon incubation with epithelial cells, thioredoxin can be observed in the cell using rocket immunoelectrophoresis [21].
• These observations suggest that glucocorticoid receptors in cytosol preparations are maintained in a reduced, steroid-binding state by a NADPH-dependent, thioredoxin-mediated reducing system [22].
• Human eosinophil cytotoxicity-enhancing factor. II. Multiple forms synthesized by U937 cells and their relationship to thioredoxin/adult T cell leukemia-derived factor [23].

Associations of trxA with chemical compounds

• The increased expression of the grxA gene in trxA gshA double mutant bacteria was mimicked in trxA single mutant cells by depletion of GSH with diethylmaleate (DEM) [24].
• Sequencing of the DNA region located upstream of the alpha-acetolactate synthase and decarboxylase (alsS-alsD) cluster of Oenococcus oeni allowed identification of an ORF, named trxA [25].
• Together they catalyze the reduction of CDP to dCDP, using dithiothreitol or reduced glutaredoxin, but not thioredoxin, as an electron donor [26].
• Asp substitutions at buried sites in two other proteins, maltose-binding protein and thioredoxin, also were shown to be severely destabilizing [27].
• Genetic manipulations of the amounts of intracellular glutathione, NADPH, alpha-ketoacids, ferredoxin, and thioredoxin indicated that none of these was the direct electron donor [28].

Physical interactions of trxA

• The high catalytic efficiency with which Nt-TrR can reduce thioredoxin implies that the attached N-terminal domain does not block access of thioredoxin to the TrR-derived Cys342-Cys345 center of Nt-TrR nor does it impede the putative conformational changes that this part of Nt-TrR is proposed to undergo during catalysis [29].

Regulatory relationships of trxA

• The strategy is to use thioredoxin mutants that are unable to support the growth of wild-type T7 phage to select for T7 revertant phage that suppress the defect in thioredoxin [30].

Other interactions of trxA

• The redox protein from PH0178 had strong thioredoxin-like activity, but no glutaredoxin activity [9].
• 3-Mercaptopyruvate sulfurtransferase of Leishmania contains an unusual C-terminal extension and is involved in thioredoxin and antioxidant metabolism [31].

Analytical, diagnostic and therapeutic context of trxA

• From the analysis of differential scanning calorimetry data alone, our model identifies the presence of a significant (>35 kJ/mol) barrier for the two-state protein thioredoxin and the absence of a barrier for BBL, a previously characterized downhill folding protein [32].
• Apoptosis contributes to myocardial ischemia/reperfusion (MI/R) injury, and both thioredoxin (Trx) and nitric oxide have been shown to exert antiapoptotic effects in vitro [19].
• Replacement of Trp28 in Escherichia coli thioredoxin by site-directed mutagenesis affects thermodynamic stability but not function [33].
• We estimated the real-time kinetics and thermodynamics of the interaction of g5p with thioredoxin (wild type and mutants) using surface plasmon resonance [34].
• Reaction between an intein-generated C-terminal thioester on E. coli maltose-binding protein (43 kDa) and an intein-generated cysteine at the N terminus of either T4 DNA ligase (56 kDa) or thioredoxin (12 kDa) resulted in the ligation of the proteins through a native peptide bond [35].

References