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Gene Review

trxA  -  thioredoxin 1

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK3773, JW5856, dasC, fip, fipA, ...
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Disease relevance of trxA


High impact information on trxA

  • The orientation of the two domains permits reduction of FAD by NADPH and oxidation of the enzyme dithiol by the protein substrate, thioredoxin [6].
  • Besides the active site, DsbC has no homology with DsbA, thioredoxin or eukaryotic protein disulfide isomerase and it could define a new subfamily of disulfide isomerases [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].
  • Although the catalytic regions of DsbA and DsbC are composed of structurally homologous thioredoxin motif domains, DsbA serves only as an oxidase in vivo, whereas DsbC catalyzes disulfide reduction and isomerization and also exhibits significant chaperone activity [9].

Chemical compound and disease context of trxA

  • The present experiments were done to elucidate the roles of thioredoxin and thioredoxin reductase system in defense against hydrogen peroxide (H2O2) in Escherichia coli [10].
  • Gently lysed E. coli tsnC 7004 cell extracts reduced CDP when supplemented with NADPH as efficiently as the parent strain E. coli B/1 despite the lack of thioredoxin, indicating the presence of another hydrogen transport system [11].
  • Fluorescence spectroscopy showed GS-Se-SG to be a very efficient oxidant of reduced thioredoxin from E. coli and kinetically superior to insulin disulfides [12].
  • This work investigates whether E. coli strains carrying mutations in the major intracellular disulfide bond-reduction systems (i.e. the thioredoxin and the glutathione/glutaredoxin pathways) allow the oxidation and folding of single chain variable fragment (scFv) antibodies in the cytoplasm [13].
  • The three-dimensional solution structure of reduced (dithiol) thioredoxin from Escherichia coli has been determined with distance and dihedral angle constraints obtained from 1H NMR spectroscopy [14].

Biological context of trxA

  • Transcriptional regulation of glutaredoxin and thioredoxin pathways and related enzymes in response to oxidative stress [15].
  • Peptides selected as FLITRX active-site fusions retain their binding specificity when made as native thioredoxin active-site loop fusions [16].
  • To reconcile the distinct catalytic activities of DsbC and DsbA, we constructed a series of chimeras comprising of the dimerization domain of DsbC, with or without the adjacent alpha-helical linker region, fused either to the first, second, third, or fifth residue of intact DsbA or to thioredoxin [9].
  • E. coli B tsnC 7004, an E. coli B/1 mutant with normal phenotype unable to replicate phage T7 DNA [Chamberlin, M. (1974)J. Virol. 14,509-516], contained no detectable level of thioredoxin when assayed with ribonucleotide reductase (2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC [11].
  • Two genes encoding thioredoxin are found on the Escherichia coli genome [17].

Anatomical context of trxA

  • We propose that DipZ, a cytoplasmic membrane protein with a thioredoxin-like domain, and thioredoxin, the product of the trxA gene, are components of a pathway for maintaining DsbC active as a protein disulfide bond isomerase [18].
  • Cytoplasmic electrons donated by thioredoxin are thought to be transferred into the periplasm via the DsbD membrane protein [19].
  • Thioredoxins have been characterized in a wide variety of prokaryotic cells, and generally show about 50% amino acid homology to Escherichia coli thioredoxin with a known three-dimensional structure [20].
  • Thus, the yield of active ATP N peroxidase can be increased 50-fold by using thioredoxin reductase negative strains, which facilitate the formation of disulfide bonds in inclusion body protein [21].
  • Peptide antigen constructs were expressed in E. coli as fusion proteins with thioredoxin and a universal tetanus toxin T-cell epitope (P2), in order to enhance the anti-peptide immune response [22].

Associations of trxA with chemical compounds

  • Induction level was as the enhanced nrdAB basal expression of trxA grxA mutants, indicating that RRase operation without Trx1 and Grx1 must lead to disturbances sensed as those caused by hydroxyurea [15].
  • The dithiol forms of thioredoxin and glutaredoxin are hydrogen donors for ribonucleotide reductase [23].
  • Electrons for disulphide bond reduction are supplied from thioredoxin in the cytoplasm via DipZ in the membrane, but can be replaced by the chemical reductant, 2-mercaptoethanesulphonic acid [24].
  • Selenodiglutathione is a highly efficient oxidant of reduced thioredoxin and a substrate for mammalian thioredoxin reductase [12].
  • However, the cysteine residues are relatively inaccessible for interaction with the substrate, thioredoxin [25].

Physical interactions of trxA


Enzymatic interactions of trxA


Regulatory relationships of trxA


Other interactions of trxA


Analytical, diagnostic and therapeutic context of trxA

  • The scheme is based on an initial separation of thioredoxin from the two reductases by affinity chromatography on agarose-bound N6-(6-aminohexyl)-adenosine 2',5'-bisphosphate (agarose-2',5'-ADP) [31].
  • This cofactor was indistinguishable from thioredoxin in molecular weight but had a slightly different isoelectric point, allowing a separation of the two types of molecules by isoelectric focusing [32].
  • Several zinc-sensitive peptides were identified, termed 'switch epitopes'. A soluble, monomeric thioredoxin loop ('Trxloop') insertion analog of a FLITRX switch epitope was constructed and its antibody binding properties were characterized by Western blots [33].
  • The high amplification of thioredoxin in these cells (i.e. 10(6) copies/cell representing 40% of total cell protein) approaches the maximum yields seen in genetically constructed cloning vehicles (Bernard, H.U., and Helinski, D.R. (1980) in Genetic Engineering (Setlow, J. K., and Hollaender, A., eds) Vol. 2, pp. 133-167, Plenum Press, New York) [34].
  • E. coli C35S Trx, in which Cys(35) was replaced with Ser, formed some adducts with MST and activated MST after treatment with DTT [35].


  1. Cloning, expression, and characterization of a novel Escherichia coli thioredoxin. Miranda-Vizuete, A., Damdimopoulos, A.E., Gustafsson, J., Spyrou, G. J. Biol. Chem. (1997) [Pubmed]
  2. Conformational and functional similarities between glutaredoxin and thioredoxins. Eklund, H., Cambillau, C., Sjöberg, B.M., Holmgren, A., Jörnvall, H., Höög, J.O., Brändén, C.I. EMBO J. (1984) [Pubmed]
  3. Molecular genetic analysis of a thioredoxin gene from Thiobacillus ferrooxidans. Powles, R.E., Deane, S.M., Rawlings, D.E. Microbiology (Reading, Engl.) (1995) [Pubmed]
  4. Crystal structure of thioredoxin-2 from Anabaena. Saarinen, M., Gleason, F.K., Eklund, H. Structure (1995) [Pubmed]
  5. Thioredoxin system in obligate anaerobe Desulfovibrio desulfuricans: Identification and characterization of a novel thioredoxin 2. Sarin, R., Sharma, Y.D. Gene (2006) [Pubmed]
  6. Twists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase. Lennon, B.W., Williams, C.H., Ludwig, M.L. Science (2000) [Pubmed]
  7. Characterization of DsbC, a periplasmic protein of Erwinia chrysanthemi and Escherichia coli with disulfide isomerase activity. Shevchik, V.E., Condemine, G., Robert-Baudouy, J. EMBO J. (1994) [Pubmed]
  8. Thionein can serve as a reducing agent for the methionine sulfoxide reductases. Sagher, D., Brunell, D., Hejtmancik, J.F., Kantorow, M., Brot, N., Weissbach, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Engineered DsbC chimeras catalyze both protein oxidation and disulfide-bond isomerization in Escherichia coli: Reconciling two competing pathways. Segatori, L., Paukstelis, P.J., Gilbert, H.F., Georgiou, G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  10. Different mechanisms of thioredoxin in its reduced and oxidized forms in defense against hydrogen peroxide in Escherichia coli. Takemoto, T., Zhang, Q.M., Yonei, S. Free Radic. Biol. Med. (1998) [Pubmed]
  11. Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione. Holmgren, A. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  12. Selenodiglutathione is a highly efficient oxidant of reduced thioredoxin and a substrate for mammalian thioredoxin reductase. Björnstedt, M., Kumar, S., Holmgren, A. J. Biol. Chem. (1992) [Pubmed]
  13. Production of functional single-chain Fv antibodies in the cytoplasm of Escherichia coli. Jurado, P., Ritz, D., Beckwith, J., de Lorenzo, V., Fernández, L.A. J. Mol. Biol. (2002) [Pubmed]
  14. Three-dimensional solution structure of the reduced form of Escherichia coli thioredoxin determined by nuclear magnetic resonance spectroscopy. Dyson, H.J., Gippert, G.P., Case, D.A., Holmgren, A., Wright, P.E. Biochemistry (1990) [Pubmed]
  15. Transcriptional regulation of glutaredoxin and thioredoxin pathways and related enzymes in response to oxidative stress. Prieto-Alamo, M.J., Jurado, J., Gallardo-Madueno, R., Monje-Casas, F., Holmgren, A., Pueyo, C. J. Biol. Chem. (2000) [Pubmed]
  16. Expression of thioredoxin random peptide libraries on the Escherichia coli cell surface as functional fusions to flagellin: a system designed for exploring protein-protein interactions. Lu, Z., Murray, K.S., Van Cleave, V., LaVallie, E.R., Stahl, M.L., McCoy, J.M. Biotechnology (N.Y.) (1995) [Pubmed]
  17. Thioredoxin 2 is involved in the oxidative stress response in Escherichia coli. Ritz, D., Patel, H., Doan, B., Zheng, M., Aslund, F., Storz, G., Beckwith, J. J. Biol. Chem. (2000) [Pubmed]
  18. An in vivo pathway for disulfide bond isomerization in Escherichia coli. Rietsch, A., Belin, D., Martin, N., Beckwith, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  19. Transfer of electrons across the cytoplasmic membrane by DsbD, a membrane protein involved in thiol-disulphide exchange and protein folding in the bacterial periplasm. Chung, J., Chen, T., Missiakas, D. Mol. Microbiol. (2000) [Pubmed]
  20. Thioredoxin and related proteins in procaryotes. Gleason, F.K., Holmgren, A. FEMS Microbiol. Rev. (1988) [Pubmed]
  21. Disulfide bond formation and folding of plant peroxidases expressed as inclusion body protein in Escherichia coli thioredoxin reductase negative strains. Teilum, K., Ostergaard, L., Welinder, K.G. Protein Expr. Purif. (1999) [Pubmed]
  22. Tandem copies of a human rotavirus VP8 epitope can induce specific neutralizing antibodies in BALB/c mice. Kovacs-Nolan, J., Mine, Y. Biochim. Biophys. Acta (2006) [Pubmed]
  23. The levels of ribonucleotide reductase, thioredoxin, glutaredoxin 1, and GSH are balanced in Escherichia coli K12. Miranda-Vizuete, A., Rodríguez-Ariza, A., Toribio, F., Holmgren, A., López-Barea, J., Pueyo, C. J. Biol. Chem. (1996) [Pubmed]
  24. The CcmE protein from Escherichia coli is a haem-binding protein. Reid, E., Eaves, D.J., Cole, J.A. FEMS Microbiol. Lett. (1998) [Pubmed]
  25. Crystal structure of Escherichia coli thioredoxin reductase refined at 2 A resolution. Implications for a large conformational change during catalysis. Waksman, G., Krishna, T.S., Williams, C.H., Kuriyan, J. J. Mol. Biol. (1994) [Pubmed]
  26. Interactions of Escherichia coli thioredoxin, the processivity factor, with bacteriophage T7 DNA polymerase and helicase. Ghosh, S., Hamdan, S.M., Cook, T.E., Richardson, C.C. J. Biol. Chem. (2008) [Pubmed]
  27. High-resolution solution structures of oxidized and reduced Escherichia coli thioredoxin. Jeng, M.F., Campbell, A.P., Begley, T., Holmgren, A., Case, D.A., Wright, P.E., Dyson, H.J. Structure (1994) [Pubmed]
  28. Characterization of Escherichia coli thioredoxins with altered active site residues. Gleason, F.K., Lim, C.J., Gerami-Nejad, M., Fuchs, J.A. Biochemistry (1990) [Pubmed]
  29. The acidic nature of the CcmG redox-active center is important for cytochrome c maturation in Escherichia coli. Edeling, M.A., Ahuja, U., Heras, B., Thöny-Meyer, L., Martin, J.L. J. Bacteriol. (2004) [Pubmed]
  30. Binding properties and solubility of single-chain T cell receptors expressed in E. coli. Schodin, B.A., Schlueter, C.J., Kranz, D.M. Mol. Immunol. (1996) [Pubmed]
  31. Purification of thioredoxin, thioredoxin reductase, and glutathione reductase by affinity chromatography. Pigiet, V.P., Conley, R.R. J. Biol. Chem. (1977) [Pubmed]
  32. Assimilatory sulfate reduction in an Escherichia coli mutant lacking thioredoxin activity. Tsang, M.L., Schiff, J.A. J. Bacteriol. (1978) [Pubmed]
  33. Investigation of the 'switch-epitope' concept with random peptide libraries displayed as thioredoxin loop fusions. Tripp, B.C., Lu, Z., Bourque, K., Sookdeo, H., McCoy, J.M. Protein Eng. (2001) [Pubmed]
  34. Amplification and purification of plasmid-encoded thioredoxin from Escherichia coli K12. Lunn, C.A., Kathju, S., Wallace, B.J., Kushner, S.R., Pigiet, V. J. Biol. Chem. (1984) [Pubmed]
  35. Thioredoxin-dependent enzymatic activation of mercaptopyruvate sulfurtransferase. An intersubunit disulfide bond serves as a redox switch for activation. Nagahara, N., Yoshii, T., Abe, Y., Matsumura, T. J. Biol. Chem. (2007) [Pubmed]
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