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Review Article

Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions

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Pages 206-245 | Received 20 Aug 2015, Accepted 11 Nov 2015, Published online: 08 Jan 2016

References

  • Netto LE, Oliveira MA, Monteiro G, Demasi AP, Cussiol JR, Discola KF, et al. Reactive cysteine in proteins: protein folding, antioxidant defense, redox signaling and more. Comp Biochem Physiol C Toxicol Pharmacol 2007;146:180–193.
  • Marino SM, Gladyshev VN. Proteomics: mapping reactive cysteines. Nat Chem Biol 2011;7:72–73.
  • Winterbourn CC, Metodiewa D. Reactivity of biologically important thiol compounds with superoxide and hydrogen peroxide. Free Radic Biol Med 1999;27:322–328.
  • Singh R, Whitesides GM. Thiol–disulfide interchange. In: Patai S, Rappoport Z, eds. Sulphur-containing functional groups. Chichester, UK: John Wiley & Sons, Inc.; 1993:633–658.
  • Aida M, Nagata, C. An ab initio MO study on the disulfide bond: properties concerning the characteristic SS dihedral angle. Theor Chim Acta 1986;70:73–80.
  • Nelson KJ, Parsonage D, Hall A, Karplus PA, Poole LB. Cysteine pKa values for the bacterial peroxiredoxin AhpC. Biochemistry 2008;47:12860–12868.
  • Parsonage D, Karplus PA, Poole LB. Substrate specificity and redox potential of AhpC, a bacterial peroxiredoxin. Proc Natl Acad Sci USA 2008;105:8209–8214.
  • Roberts BR, Wood ZA, Jönsson TJ, Poole LB, Karplus PA. Oxidized and synchrotron cleaved structures of the disulfide redox center in the N-terminal domain of Salmonella typhimurium AhpF. Protein Sci 2005;14:2414–2420.
  • Nelson JW, Creighton TE. Reactivity and ionization of the active site cysteine residues of DsbA, a protein required for disulfide bond formation in vivo. Biochemistry 1994;33:5974–5983.
  • Grauschopf U, Winther, JR, Korber P, Zander T, Dallinger P, Bardwell JCA. Why is DsbA such an oxidizing disulfide catalyst? Cell 1995;83:947–955.
  • Wunderlich M, Glockshuber R. Redox properties of protein disulfide isomerase (DsbA) from Escherichia coli. Protein Sci 1993;2:717–726.
  • Hirasawa M, Schürmann P, Jacquot JP, Manieri W, Jacquot P, Keryer E, et al. Oxidation-reduction properties of chloroplast thioredoxins, ferredoxin: thioredoxin reductase, and thioredoxin f-regulated enzymes. Biochemistry 1999;38:5200–5205.
  • Foloppe N, Nilsson L. The glutaredoxin -C-P-Y-C- motif: influence of peripheral residues. Structure 2004;12:289–300.
  • Åslund F, Berndt KD, Holmgren A. Redox potentials of glutaredoxins and other thiol-disulfide oxidoreductases of the thioredoxin superfamily determined by direct protein-protein redox equilibria. J Biol Chem 1997;272:30780–30786.
  • Discola KF, Oliveira MA, Cussiol JRR, Monteiro G, Bárcena JA, Porras P, et al. Structural aspects of the distinct biochemical properties of glutaredoxin 1 and glutaredoxin 2 from Saccharomyces cerevisiae. J Mol Biol 2009;385:889–901.
  • Veine DM, Arscott LD, Williams CH Jr. Redox potentials for yeast, Escherichia coli and human glutathione reductase relative to the NAD+/NADH redox couple: enzyme forms active in catalysis. Biochemistry 1998;37:15575–15582.
  • Sahlman L, Williams CH Jr. Lipoamide dehydrogenase from Escherichia coli. Steady-state kinetics of the physiological reaction. J Biol Chem 1989;264:8039–8045.
  • Schultz PG, Au KG, Walsh CT. Directed mutagenesis of the redox-active disulfide in the flavoenzyme mercuric ion reductase. Biochemistry 1985;24:6840–6848.
  • Fox B, Walsh CT. Mercuric reductase. Purification and characterization of a transposon-encoded flavoprotein containing an oxidation-reduction-active disulfide. J Biol Chem 1982;257:2498–2503.
  • Karala AR, Lappi AK, Ruddock LW. Modulation of an active-site cysteine pKa allows PDI to act as a catalyst of both disulfide bond formation and isomerization. J Mol Biol 2010;396:883–892.
  • Chambers JE, Tavender TJ, Oka OB, Warwood S, Knight D, Bulleid NJ. The reduction potential of the active site disulfides of human protein disulfide isomerase limits oxidation of the enzyme by Ero1α. J Biol Chem 2010;285:29200–29207.
  • Reutimann H, Straub B, Luisi PL, Holmgren A. A conformational study of thioredoxin and its tryptic fragments. J Biol Chem 1981;256:6796–6803.
  • Chivers PT, Prehoda KE, Volkman BF, Kim BM, Markley JL, Raines RT. Microscopic pKa values of Escherichia coli thioredoxin. Biochemistry 1997;36:14985–14991.
  • Mössner E, Huber-Wunderlich M, Rietsch A, Beckwith J, Glockshuber R, Åslund F. Importance of redox potential for the in vivo function of the cytoplasmic disulfide reductant thioredoxin from Escherichia coli. J Biol Chem 1999;274:25254–25259.
  • Mason JT, Kim SK, Knaff DB, Wood MJ. Thermodynamic basis for redox regulation of the Yap1 signal transduction pathway. Biochemistry 2006;45:13409–13417.
  • O'Donnell ME, Williams CH Jr. Proton stoichiometry in the reduction of the FAD and disulfide of Escherichia coli thioredoxin reductase. Evidence for a base at the active site. J Biol Chem 1983;258:13795–13805.
  • Williams CH, Jr. Mechanism and structure of thioredoxin reductase from Escherichia coli. FASEB J 1995;13:1267–1276.
  • Reckenfelderbaumer N, Krauth-Siegel RL. Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. J Biol Chem 2002;277:17548–17555.
  • Gilbert HF. Molecular and cellular aspects of thiol-disulfide exchange. Adv Enzymol Relat Areas Mol Biol 1990;63:69–172.
  • Laurent TC, Moore EC, Reichard P. Enzymatic synthesis of deoxyribonucleotides. IV. Isolation and characterization of thioredoxin the hydrogen donor from Escherichia coli. J Biol Chem 1964;239:3436–3444.
  • Boschi-Muller S, Azza S, Sanglier-Cianferani S, Talfournier F, Van Dorsselear A, Branlant G. A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of peptide methionine sulfoxide reductase from Escherichia coli. J Biol Chem 2000;275:35908–35913.
  • Lowther WT, Brot N, Weissbach H, Honek HF, Matthews, B. Thiol-disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase. Proc Natl Acad Sci USA 2000;97:6463–6468.
  • Chae HZ, Chung SJ, Rhee SG. Thioredoxin-dependent peroxide reductase from yeast. J Biol Chem 1994;269:27670–27678.
  • Hansen RE, Roth D, Winther JR. Quantifying the global cellular thiol-disulfide status. Proc Natl Acad Sci USA 2009;106:422–427.
  • Jensen KS, Hansen RE, Winther JR. Kinetic and thermodynamic aspects of cellular thiol-disulfide redox regulation. Antioxid Redox Signal 2009;11:1047–1058.
  • Nagy P. Kinetics and mechanisms of thiol–disulfide exchange covering direct substitution and thiol oxidation-mediated pathways. Antioxid Redox Sign 2013;18:1623–1641.
  • Ferrer-Sueta G, Manta B, Botti H, Radi R, Trujillo M, Denicola A. Factors affecting protein thiol reactivity and specificity in peroxide reduction. Chem Res Toxicol 2011;24:434–450.
  • Trujillo M, Clippe A, Manta B, Ferrer-Sueta G, Smeets A, Declercq JP, et al. Pre-steady state kinetic characterization of human peroxiredoxin 5: taking advantage of Trp84 fluorescence increase upon oxidation. Arch Biochem Biophys 2007;467:95–106.
  • Bulaj G, Kortemme T, Goldenberg DP. Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry 1998;37:8965–8972.
  • Szajewski RP, Whitesides GM. Rate constants and equilibrium constants for thiol–disulfide interchange reactions involving oxidized glutathione. J Am Chem Soc 1980;102:2011–2026.
  • Wilson JM, Bayer RJ, Hupe DJ. Structure-reactivity correlations for the thiol-disulfide interchange reaction. J Am Chem Soc 1977;99:7922–7926.
  • DeCollo TV, Lees WJ. Effects of aromatic thiols on thiol-disulfide interchange reactions that occur during protein folding. J Org Chem 2001;66:4244–4249.
  • Fernandes PA, Ramos MJ. Theoretical insights into the mechanism for thiol/disulfide exchange. Chemistry 2004;10:257–266.
  • Hansen RE, Østergaard H, Winther JR. Increasing the reactivity of an artificial dithiol-disulfide pair through modification of the electrostatic milieu. Biochemistry 2005;44:5899–5906.
  • Hupe DJ, Wu D. Effect of charged substituents on rates of the thiol-disulfide interchange reaction. J Org Chem 1980;45:3100–3103.
  • Snyder GH, Cennerazzo MJ, Karalis AJ, Field D. Electrostatic influence of local cysteine environments on disulfide exchange kinetics. Biochemistry 1981;20:6509–6519.
  • Snyder GH. Free energy relationships for thiol-disulfide interchange reactions between charged molecules in 50% methanol. J Biol Chem 1984;259:7468–7472.
  • Singh R, Whitesides GM. Degenerate intermolecular thiolate-disulfide interchange involving cyclic five-membered disulfides is faster by ∼103 than that involving six- or seven-membered disulfides. J Am Chem Soc 1990;112:6304–6309.
  • Sideris DP, Petrakis N, Katrakili N, Mikropoulou D, Gallo A, Ciofi-Baffoni S, et al. A novel intermembrane space-targeting signal docks cysteines onto Mia40 during mitochondrial oxidative folding. J Cell Biol 2009;187:1007–1022.
  • Wunderlich M, Glockshuber R. In vivo control of redox potential during protein folding catalyzed by bacterial protein disulfide-isomerase (DsbA). J Biol Chem 1993;268:24547–24550
  • Dadlez M, Kim PS. Rapid formation of the native 14-38 disulfide bond in the early stages of BPTI folding. Biochemistry 1996;35:16153–16164.
  • Demasi M, Piassa Filho GM, Castro LM, Ferreira JC, Rioli V, Ferro ES. Oligomerization of the cysteinyl-rich oligopeptidase EP24.15 is triggered by S-glutathionylation. Free Radic Biol Med 2008;44:1180–1190.
  • Creighton TE. The two-disulphide intermediates and the folding pathway of reduced pancreatic trypsin inhibitor. J Mol Biol 1975;95:167–199.
  • Holmgren A. Thioredoxin catalyzes the reduction of insulin disulfides by dithiothreitol and dihydrolipoamide. J Biol Chem 1979;254:9627–9632.
  • Katti SK, LeMaster DM, Eklund H. Crystal structure of thioredoxin from Escherichia coli at 1.68 Å resolution. J Mol Biol 1990;212:167–184.
  • Cheng Z, Zhang J, Ballou DP, Williams CH, Jr. Reactivity of thioredoxin as a protein thiol-disulfide oxidoreductase. Chem Rev 2011;111:5768–5783.
  • Gruber CW, Cemazar M, Heras B, Martin JL, Craik DJ. Protein disulfide isomerase: the structure of oxidative folding. Trends Biochem Sci 2006;31:455–464.
  • Ingles-Prieto A, Ibarra-Molero B, Delgado-Delgado A, Perez-Jimenez R, Fernandez JM, Gaucher EA, et al. Conservation of protein structure over four billion years. Structure 2013;21:1690–1697.
  • Holmgren A. Tryptophan fluorescence study of conformational transitions of the oxidized and reduced form of thioredoxin. J Biol Chem 1972;247:1992–1998.
  • Lee DY, Ahn BY, Kim KS. A thioredoxin from the hyperthermophilic archaeon Methanococcus jannaschii has a glutaredoxin-like fold but thioredoxin-like activities. Biochemistry 2000;39:6652–6659.
  • Mössner E, Huber-Wunderlich M, Glockshuber R. Characterization of Escherichia coli thioredoxin variants mimicking the active-sites of other thiol/disulfide oxidoreductases. Protein Sci 1998;7:1233–1244.
  • Li H, Hanson C, Fuchs JA, Woodward C, Thomas GJ Jr. Determination of the pKa values of active-center cysteines, cysteines-32 and -35, in Escherichia coli thioredoxin by Raman spectroscopy. Biochemistry 1993;32:5800–5808.
  • Vohník S, Hanson C, Tuma R, Fuchs JA, Woodward C, Thomas GJ, Jr. Conformation, stability, and active-site cysteine titrations of Escherichia coli D26A thioredoxin probed by Raman spectroscopy. Protein Sci 1998;7:193–200.
  • Chivers PT, Laboissiere MC, Raines RT. The CXXC motif: imperatives for the formation of native disulfide bonds in the cell. EMBO J 1996;15:2659–2667.
  • Forman-Kay JD, Clore GM, Gronenborn AM. Relationship between electrostatics and redox function in human thioredoxin: characterization of pH titration shifts using two-dimensional homo- and heteronuclear NMR. Biochemistry 1992;31:3442–3452.
  • Krimm I, Lemaire S, Ruelland E, Miginiac-Maslow M, Jaquot JP, Hirasawa M, et al. The single mutation Trp35→Ala in the 35-40 redox site of Chlamydomonas reinhardtii thioredoxin h affects its biochemical activity and the pH dependence of C36-C39 1H-13C NMR. Eur J Biochem 1998;255:185–195.
  • Dyson HJ, Jeng MF, Tennant LL, Slaby I, Lindell M, Cui DS, et al. Effects of buried charged groups on cysteine thiol ionization and reactivity in Escherichia coli thioredoxin: structural and functional characterization of mutants of Asp 26 and Lys 57. Biochemistry 1997;36:2622–2636.
  • Takahashi N, Creighton TE. On the reactivity and ionization of the active site cysteine residues of Escherichia coli thioredoxin. Biochemistry 1996;35:8342–8353.
  • Roos G, Foloppe N, Van Laer K, Wyns L, Nilsson L, Geerlings P, Messens J. How thioredoxin dissociates its mixed disulfide. PLoS Comput Biol 2009;5:e1000461.
  • Graminski GF, Kubo Y, Armstrong RN. Spectroscopic and kinetic evidence for the thiolate anion of glutathione at the active site of glutathione S-transferase. Biochemistry 1989;28:3562–3568.
  • Moutevelis E, Warwicker J. Prediction of pKa and redox properties in the thioredoxin superfamily. Protein Sci 2004;13:2744–2752.
  • Biterova EI, Turanov AA, Gladyshev VN, Barycki JJ. Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism. Proc Natl Acad Sci USA 2005;102:15018–15023.
  • Lennon BW, Williams CHJr, Ludwig ML. Twists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase. Science 2000;289:1190–1194.
  • Lillig CH, Holmgren A. Thioredoxin and related molecules – from biology to health and disease. Antioxid Redox Signaling 2007;9:25–47.
  • Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G. Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. Proc Natl Acad Sci USA 2001;98:9533–9538.
  • Shaked Z, Szajewski RP, Whitesides GM. Rates of thiol-disulfide interchange reactions involving proteins and kinetic measurements of thiol pKa values. Biochemistry 1980;19:4156–4166.
  • LeMaster DM. Structural determinants of the catalytic reactivity of the buried cysteine of Escherichia coli thioredoxin. Biochemistry 1996;35:14876–14881.
  • Mössner E, Iwai H, Glockshuber R. Influence of the pKa value of the buried, active-site cysteine on the redox properties of thioredoxin-like oxidoreductases. FEBS Lett 2000;477:21–26.
  • Kortemme T, Creighton TE. Ionization of cysteine residues at the termini of model alpha-helical peptides. Relevance to unusual thiol pKa values in proteins of the thioredoxin family. J Mol Biol 1995;253:799–812.
  • Roos G, Foloppe N, Messens J. Understanding the pKa of redox cysteines: the key role of hydrogen bonding. Antioxid Redox Signal 2013;18:94–127.
  • Carvalho AT, Swart M, van Stralen JN, Fernandes PA, Ramos MJ, Bickelhaupt FM. Mechanism of thioredoxin-catalyzed disulfide reduction. Activation of the buried thiol and role of the variable active-site residues. Phys Chem B 2008;112:2511–2523.
  • Wynn R, Cocco MJ, Richards FM. Mixed disulfide intermediates during the reduction of disulfides by Escherichia coli thioredoxin. Biochemistry 1995;34:11807–11813.
  • Chivers PT, Raines RT. General acid/base catalysis in the active site of Escherichia coli thioredoxin. Biochemistry 1997;36:15810–15816.
  • Menchise V, Corbier C, Didierjean C, Saviano M, Benedetti E, Jacquot JP, Aubry A. Crystal structure of the wild-type and D30A mutant thioredoxin h of Chlamydomonas reinhardtii and implications for the catalytic mechanism. Biochem J 2001;359:65–75.
  • Dyson HJ, Tennant LL, Holmgren A. Proton-transfer effects in the active-site region of Escherichia coli thioredoxin using two-dimensional 1H NMR. Biochemistry 1991;30:4262–4268.
  • Langsetmo K, Fuchs JA, Woodward C. The conserved, buried aspartic acid in oxidized Escherichia coli thioredoxin has a pKa of 7.5. Its titration produces a related shift in global stability. Biochemistry 1991;30:7603–7609.
  • LeMaster DM, Springer PA, Unkefer CJ. The role of the buried aspartate of Escherichia coli thioredoxin in the activation of the mixed disulfide intermediate. J Biol Chem 1997;272:29998–30001.
  • Krause G, Holmgren AA. Substitution of the conserved tryptophan 31 in Escherichia coli thioredoxin by site-directed mutagenesis and structure-function analysis. J Biol Chem 1991;266:4056–4066.
  • Cruzeiro-Silva C, Gomes-Neto F, Machado LE, Miyamoto CA, Pinheiro AS, Correa-Pereira N, et al. Hydration and conformational equilibrium in yeast thioredoxin 1: implication for H(+) exchange. Biochemistry 2014;53:2890–2902.
  • Iqbal A, Gomes-Neto F, Myiamoto CA, Valente AP, Almeida FC. Dissection of the water cavity of yeast thioredoxin 1: the effect of a hydrophobic residue in the cavity. Biochemistry 2015;54:2429–2442.
  • Kelley RF, Richards FM. Replacement of proline-76 with alanine eliminates the slowest kinetic phase in thioredoxin folding. Biochemistry 1987;26:6765–6774.
  • Langsetmo K, Fuchs J, Woodward C. Escherichia coli thioredoxin folds into two compact forms of different stability to urea denaturation. Biochemistry 1989;28:3211–3220.
  • Maeda K, Hägglund P, Finnie C, Svensson B, Henriksen A. Structural basis for target protein recognition by the protein disulfide reductase thioredoxin. Structure 2006;14:1701–1710.
  • Martin JL. Thioredoxin – a fold for all reasons. Structure 1995;3:245–250.
  • Mora-García S, Rodríguez-Suárez R, Wolosiuk RA. Role of electrostatic interactions on the affinity of thioredoxin for target proteins. Recognition of chloroplast fructose-1, 6-bisphosphatase by mutant Escherichia coli thioredoxins. J Biol Chem 1998;273:16273–16280.
  • Oliveira MA, Discola KF, Alves SV, Medrano FJ, Guimarães BG, Netto LE. Insights into the specificity of thioredoxin reductase-thioredoxin interactions. A structural and functional investigation of the yeast thioredoxin system. Biochemistry 2010;49:3317–3326.
  • Schwarz O, Schürmann P, Strotmann H. Kinetics and thioredoxin specificity of thiol modulation of the chloroplast H+-ATPase. J Biol Chem 1997;272:16924–16927.
  • Wahl MC, Irmler A, Hecker B, Schirmer RH, Becker K. Comparative structural analysis of oxidized and reduced thioredoxin from Drosophila melanogaster. J Mol Biol 2005;345:1119–1130.
  • Geck MK, Larimer FW, Hartman FC. Identification of residues of spinach thioredoxin f that influence interactions with target enzymes. J Biol Chem 1996;271:24736–24740.
  • Knaff DB. Oxidation-reduction properties of thioredoxins and thioredoxin-regulated enzymes. Physiol Plant 2000;110:309–313.
  • Jacquot JP, Lopez-Jaramillo J, Chueca A, Cherfils J, Lemaire S, Chedozeau B, et al. High-level expression of recombinant pea chloroplast fructose-1,6-bisphosphatase and mutagenesis of its regulatory site. Eur J Biochem 1995;229:675–681.
  • Villeret V, Huang S, Zhang Y, Xue Y, Lipscomb WN. Crystal structure of spinach chloroplast fructose-1,6-bisphosphatase at 2.8 Å resolution. Biochemistry 1995;34:4299–4306.
  • López-Jaramillo J, Chueca A, Jacquot JP, Hermoso R, Lázaro JJ, Sahrawy M, López Gorgé J. High-yield expression of pea thioredoxin m and assessment of its efficiency in chloroplast fructose-1,6-bisphosphatase activation. Plant Physiol 1997;114:1169–1175.
  • Balmer Y, Koller A, Val GD, Schürmann P, Buchanan BB. Proteomics uncovers proteins interacting electrostatically with thioredoxin in chloroplasts. Photosynth Res 2004;79:275–280.
  • Braun H, Lichter A, Haberlein I. Kinetic evidence for protein complexes between thioredoxin and NADP-malate dehydrogenase and presence of a thioredoxin binding site at the N-terminus of the enzyme. Eur J Biochem 1996;240:781–788.
  • Haberlein I, Vogeler B. Completion of the thioredoxin reaction mechanism: kinetic evidence for protein complexes between thioredoxin and fructose 1,6-bisphosphatase. Biochim Biophys Acta 1995;1253:169–174.
  • Cejudo FJ, Ferrández J, Cano B, Puerto-Galán L, Guinea M. The function of the NADPH thioredoxin reductase C-2-Cys peroxiredoxin system in plastid redox regulation and signalling. FEBS Lett 2012;586:2974–2980.
  • Poole LB. Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases. Arch Biochem Biophys 2005;433:240–254.
  • Meyer Y, Buchanan BB, Vignols F, Reichheld JP. Thioredoxins and glutaredoxins: unifying elements in redox biology. Annu Rev Genet 2009;43:335–367.
  • Horta BB, Oliveira MA, Discola KF, Cussiol JR, Netto LES. Structural and biochemical characterization of peroxiredoxin Qβ from Xylella fastidiosa: catalytic mechanism and high reactivity. J Biol Chem 2010;285:16051–16065.
  • Amorim GC, Pinheiro AS, Netto LES, Valente AP, Almeida FC. NMR solution structure of the reduced form of thioredoxin 2 from Saccharomyces cerevisiae. J Biomol NMR 2007;38:99–104.
  • Pinheiro AS, Amorim GC, Netto LES, Almeida FC, Valente AP. NMR solution structure of the reduced form of thioredoxin 1 from Saccharomyces cerevisiae. Proteins 2008;70:584–587.
  • Berndt C, Schwenn JD, Lillig CH. The specificity of thioredoxins and glutaredoxins is determined by electrostatic and geometric complementarity. Chem Sci 2015;6:7049–7058.
  • Lin TY. G33D mutant thioredoxin primarily affects the kinetics of reaction with thioredoxin reductase. Probing the structure of the mutant protein. Biochemistry 1999;38:15508–15513.
  • Lin TY, Chen TS. A positive charge at position 33 of thioredoxin primarily affects its interaction with other proteins but not redox potential. Biochemistry 2004;43:945–952.
  • Perez-Jimenez R, Li J, Kosuri P, Sanchez-Romero I, Wiita AP, Rodriguez-Larrea D, et al. Diversity of chemical mechanisms in thioredoxin catalysis revealed by single-molecule force spectroscopy. Nat Struct Mol Biol 2009;16:890–896.
  • Palde PB, Carroll KS. A universal entropy-driven mechanism for thioredoxin-target recognition. Proc Natl Acad Sci USA 2015;112:7960–7965.
  • Tairum CA, Oliveira MA, Horta BB, Zara FJ, Netto LES. Disulfide biochemistry in 2-cys peroxiredoxin: requirement of Glu50 and Arg146 for the reduction of yeast Tsa1 by thioredoxin. J Mol Biol 2012;424:28–41.
  • Watson WH, Pohl J, Montfort WR, Stuchlik O, Reed MS, Powis G, Jones DP. Redox potential of human thioredoxin 1 and identification of a second dithiol/disulfide motif. J Biol Chem 2003;278:33408–33415.
  • Du Y, Zhang H, Zhang X, Lu J, Holmgren A. Thioredoxin 1 is inactivated due to oxidation induced by peroxiredoxin under oxidative stress and reactivated by the glutaredoxin system. J Biol Chem 2013;288:32241–32247.
  • Casagrande S, Bonetto V, Fratelli M, Gianazza E, Eberini I, Massignan T, et al. Glutathionylation of human thioredoxin: a possible crosstalk between the glutathione and thioredoxin systems. Proc Natl Acad Sci USA 2002;99:9745–9749.
  • Andersen JF, Sanders DA, Gasdaska JR, Weichsel A, Powis G, Montfort WR. Human thioredoxin homodimers: regulation by pH, role of aspartate 60, and crystal structure of the aspartate 60 –> asparagine mutant. Biochemistry 1997;36:13979–13988.
  • Weichsel A, Gasdaska JR, Powis G, Montfort WR. Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer. Structure 1996;4:735–751.
  • Wang P, Wu Y, Li X, Ma X, Zhong L. Thioredoxin and thioredoxin reductase control tissue factor activity by thiol redox-dependent mechanism. J Biol Chem 2013;288:3346–3358.
  • Lee S, Kim SM, Lee RT. Thioredoxin and thioredoxin target proteins: from molecular mechanisms to functional significance. Antioxid Redox Signal 2013;18:1165–1207.
  • Atkinson HJ, Babbitt PC. An atlas of the thioredoxin fold class reveals the complexity of function-enabling adaptations. PLoS Comput Biol 2009;10:e1000541.
  • Berndt C, Lillig CH, Holmgren A. Thioredoxins and glutaredoxins as facilitators of protein folding. Biochim Biophys Acta 2008;1783:641–650.
  • Holmgren A. Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione. Proc Natl Acad Sci USA 1976;73:2275–2279.
  • Askelöf P, Axelsson K, Eriksson S, Mannervik B. Mechanism of action of enzymes catalyzing thiol-disulfide interchange. Thioltransferases rather than transhydrogenases. FEBS Lett 1974;38:263–267.
  • Gallogly MM, Starke DW, Mieyal JJ. Mechanistic and kinetic details of catalysis of thiol-disulfide exchange by glutaredoxins and potential mechanisms of regulation. Antioxid Redox Signal 2009;11:1059–1081.
  • Lillig CH, Berndt C. Glutaredoxins in thiol/disulfide exchange. Antioxid Redox Signal 2013;18:1654–1665.
  • Bushweller JH, Billeter M, Holmgren A, Wüthrich K. The nuclear magnetic resonance solution structure of the mixed disulfide between Escherichia coli glutaredoxin (C14S) and glutathione. J Mol Biol 1994;235:1585–1597.
  • Håkansson KO, Winther JR. Structure of glutaredoxin Grx1p C30S mutant from yeast. Acta Crystallogr D Biol Crystallogr 2007;63:288–294.
  • Nordstrand K, Åslund F, Holmgren A, Otting G, Berndt KD. NMR structure of Escherichia coli glutaredoxin 3-glutathione mixed disulfide complex: implications for the enzymatic mechanism. J Mol Biol 1999;286:541–552.
  • Yang Y, Jao SC, Nanduri S, Starke DW, Mieyal JJ, Qin J. Reactivity of the human thioltransferase (glutaredoxin) C7S, C25S, C78S, C82S mutant and NMR solution structure of its glutathionyl mixed disulfide intermediate reflect catalytic specificity. Biochemistry 1998;37:17145–17156.
  • Yu J, Zhang NN, Yin PD, Cui PX, Zhou CZ. Glutathionylation-triggered conformational changes of glutaredoxin Grx1 from the yeast Saccharomyces cerevisiae. Proteins 2008;72:1077–1083.
  • Deponte M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 2013;1830:3217–3266.
  • Collet JF, D'Souza JC, Jakob U, Bardwell JC. Thioredoxin 2, an oxidative stress-induced protein, contains a high affinity zinc binding site. J Biol Chem 2003;278:45325–45332.
  • Bushweller JH, Åslund F, Wüthrich K, Holmgren A. Structural and functional characterization of the mutant Escherichia coli glutaredoxin (C14–S) and its mixed disulfide with glutathione. Biochemistry 1992;31:9288–9293.
  • Berardi MJ, Bushweller JH. Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction. J Mol Biol 1999;292:151–161.
  • Bräutigam L, Schütte LD, Godoy JR, Prozorovski T, Gellert M, Hauptmann G, et al. Vertebrate-specific glutaredoxin is essential for brain development. Proc Natl Acad Sci USA 2011;108:20532–20537.
  • Gellert M, Venz S, Mitlöhner J, Cott C, Hanschmann EM, Lillig CH. Identification of a dithiol-disulfide switch in collapsin response mediator protein 2 (CRMP2) that is toggled in a model of neuronal differentiation. J Biol Chem 2013;288:35117–35125.
  • Gallogly MM, Starke DW, Leonberg AK, Ospina SM, Mieyal JJ. Kinetic and mechanistic characterization and versatile catalytic properties of mammalian glutaredoxin 2: implications for intracellular roles. Biochemistry 2008;47:11144–11157.
  • Rouhier N, Gelhaye E, Jacquot JP. Exploring the active site of plant glutaredoxin by site-directed mutagenesis. FEBS Lett 2002;511:145–149.
  • Yang YF, Wells WW. Catalytic mechanism of thioltransferase. J Biol Chem 1991;266:12766–12771.
  • Johansson C, Kavanagh KL, Gileadi O, Oppermann U. Reversible sequestration of active site cysteines in a 2Fe-2S-bridged dimer provides a mechanism for glutaredoxin 2 regulation in human mitochondria. J Biol Chem 2007;282:3077–3082.
  • Lundberg M, Holmgren A, Johansson M. Human glutaredoxin 2 affinity tag for recombinant peptide and protein purification. Protein Expr Purif 2006;45:37–42.
  • Bräutigam L, Jensen LD, Poschmann G, Nyström S, Bannenberg S, Dreij K, et al. Glutaredoxin regulates vascular development by reversible glutathionylation of sirtuin 1. Proc Natl Acad Sci USA 2013;110:20057–20062.
  • Berndt C, Poschmann G, Stühler K, Holmgren A, Bräutigam L. Zebrafish heart development is regulated via glutaredoxin 2 dependent migration and survival of neural crest cells. Redox Biol 2014;2:673–678.
  • Gravina SA, Mieyal JJ. Thioltransferase is a specific glutathionyl mixed disulfide oxidoreductase. Biochemistry 1993;32:3368–3376.
  • Jensen KS, Pedersen JT, Winther JR, Teilum K. The pKa value and accessibility of cysteine residues are key determinants for protein substrate discrimination by glutaredoxin. Biochemistry 2014;53:2533–2540.
  • Srinivasan U, Mieyal PA, Mieyal JJ. pH profiles indicative of rate-limiting nucleophilic displacement in thioltransferase catalysis. Biochemistry 1997;36:3199–3206.
  • Holmgren A, Åslund F. Glutaredoxin. Methods Enzymol 1995;252:283–292.
  • Begas P, Staudachera V, Deponte M. Systematic re-evaluation of the bis(2-hydroxyethyl)disulfide (HEDS) assay reveals an alternative mechanism and activity of glutaredoxins. Chem Sci 2015;6;3788–3796.
  • Eckers E, Bien M, Stroobant V, Herrmann JM, Deponte M. Biochemical characterization of dithiol glutaredoxin 8 from Saccharomyces cerevisiae: the catalytic redox mechanism redox. Biochemistry 2009;48:1410–1423.
  • Johansson C, Lillig CH, Holmgren A. Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. J Biol Chem 2004;279:7537–7543.
  • Netto LES, Oliveira MA. Site-directed mutagenesis as a tool to characterize specificity in thiol based redox interactions between proteins and substrates. In: Figurski D, ed. Genetic manipulation of DNA and protein – examples from current research. Croatia: InTech; 2013:91–106.
  • Fernandes AP, Holmgren A. Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system. Antioxid Redox Signal 2004;6:63–74.
  • Jao SC, English Ospina SM, Berdis AJ, Starke DW, Post CB, Mieyal JJ. Computational and mutational analysis of human glutaredoxin (thioltransferase): probing the molecular basis of the low pKa of cysteine 22 and its role in catalysis. Biochemistry 2006;45:4785–4796.
  • Sun C, Berardi MJ, Bushweller JH. The NMR solution structure of human glutaredoxin in the fully reduced form. J Mol Biol 1998;280:687–701.
  • Demasi M, Netto LE, Silva GM, Hand A, de Oliveira CL, Bicev RN, et al. Redox regulation of the proteasome via S-glutathionylation. Redox Biol 2013;2:44–51.
  • Gallogly MM, Mieyal JJ. Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stress. Curr Opin Pharmacol 2007;7:381–391.
  • Grek CL, Zhang J, Manevich Y, Townsend DM, Tew KD. Causes and consequences of cysteine S-glutathionylation. J Biol Chem 2013;288:26497–26504.
  • Couturier J, Przybyla-Toscano J, Roret T, Didierjean C, Rouhier N. The roles of glutaredoxins ligating Fe-S clusters: sensing, transfer or repair functions? Biochim Biophys Acta 2015;1853:1513–1527.
  • Flohé L. The trypanothione system and the opportunities it offers to create drugs for the neglected kinetoplast diseases. Biotechnol Adv 2012;30:294–301.
  • Krauth-Siegel RL, Comini MA. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochem Biophys Acta 2008;1780:1236–1248.
  • Fairlamb AH, Blackburn P, Ulrich P, Chait BT, Cerami A. Trypanothione: a novel bis (glutathionyl) spermidine cofactor for glutathione reductase in trypanosomatids. Science 1985;227:1485–1487.
  • Moutiez M, Meziane-Cherie D, Aumercier M, Sergheraert C, Tartar A. Compared reactivities of trypanothione and glutathione in conjugation reactions. Chem Pharm Bull 1994;42:2641–2644.
  • Hofmann B, Budde H, Bruns K, Guerrero SA, Kalisz HM, Menge U, et al. Structures of tryparedoxins revealing interaction with trypanothione. Biol Chem 2001;382:459–471.
  • Montemartini M, Kalisz HM, Kiess M, Nogoceke E, Singh M, Steinert P, Flohé L. Sequence, heterologous expression and functional characterization of a novel tryparedoxin from Crithidia fasciculata. Biol Chem 1998;379:1137–1142.
  • Krumme D, Budde H, Hecht HJ, Menge U, Ohlenschlager O, Ross A, et al. NMR studies of the interaction of tryparedoxin with redox-inactive substrate homologues. Biochemistry 2003;42:14720–14728.
  • Steinert P, Plank-Schumacher K, Montemartini M, Hecht HJ, Flohé L. Permutation of the active site motif of tryparedoxin 2. Biol Chem 2000;381:211–219.
  • Budde H, Flohé L, Hecht HJ, Hofmann B, Stehr M, Wissing J, Lünsdorf H. Kinetics and redox-sensitive oligomerisation reveal negative subunit cooperativity in tryparedoxin peroxidase of Trypanosoma brucei brucei. Biol Chem 2003;384:619–633.
  • Piñeyro MD, Pizarro JC, Lema F, Pritsch O, Cayota A, Bentley GA, Robello C. Crystal structure of the tryparedoxin peroxidase from the human parasite Trypanosoma cruzi. J Struct Biol 2005;150:11–22.
  • Xiao R, Lundström-Ljung J, Holmgren A, Gilbert HF. Catalysis of thiol/disulfide exchange. Glutaredoxin 1 and protein-disulfide isomerase use different mechanisms to enhance oxidase and reductase activities. J Biol Chem 2005;280:21099–21106.
  • Hernández G, Anderson JS, LeMaster DM. Electrostatic stabilization and general base catalysis in the active site of the human protein disulfide isomerase a domain monitored by hydrogen exchange. Chembiochem 2008;9:768–778.
  • Guddat LW, Bardwell JC, Martin JL. Crystal structures of reduced and oxidized DsbA: investigation of domain motion and thiolate stabilization. Structure 1998;6:757–767.
  • Wang C, Li W, Ren J, Fang J, Ke H, Gong W, et al. Structural insights into the redox-regulated dynamic conformations of human protein disulfide isomerase. Antioxid Redox Signal 2013;19:36–45.
  • Depuydt M, Messens J, Collet JF. How proteins form disulfide bonds. Antioxid Redox Signal 2011;15:49–66.
  • Joelson T, Sjöberg BM, Eklund H. Modifications of the active center of T4 thioredoxin by site-directed mutagenesis. J Biol Chem 1990;265:3183–3188.
  • Krause G, Lundström J, Barea JL, Pueyo de la Cuesta C, Holmgren A. Mimicking the active site of protein disulfide-isomerase by substitution of proline 34 in Escherichia coli thioredoxin. J Biol Chem 1991;266:9494–9500.
  • Chivers PT, Prehoda KE, Raines RT. The CXXC motif: a rheostat in the active site. Biochemistry 1997;36:4061–4066.
  • Ren G, Stephan D, Xu Z, Zheng Y, Tang D, Harrison RS, et al. Properties of the thioredoxin fold superfamily are modulated by a single amino acid residue. J Biol Chem 2009;284:10150–10159.
  • Kadokura H, Tian H, Zander T, Bardwell JC, Beckwith J. Snapshots of DsbA in action: detection of proteins in the process of oxidative folding. Science 2004;303:534–537.
  • Su D, Berndt C, Fomenko DE, Holmgren A, Gladyshev VN. A conserved cis-proline precludes metal binding by the active site thiolates in members of the thioredoxin family of proteins. Biochemistry 2007;46:6903–6910.
  • Inaba K, Murakami S, Suzuki M, Nakagawa A, Yamashita E, Okada K, Ito K. Crystal structure of the DsbB-DsbA complex reveals a mechanism of disulfide bond generation. Cell 2006;127:789–801.
  • Bewley KD, Dey M, Bjork RE, Mitra S, Chobot SE, Drennan CL, Elliott SJ. Rheostat re-wired: alternative hypotheses for the control of thioredoxin reduction potentials. PLoS One 2015;10:e0122466.
  • Flohé L. The fairytale of the GSSG/GSH redox potential. Biochim Biophys Acta 2013;1830:3139–3142.
  • Debarbieux L, Beckwith J. On the functional interchangeability, oxidant versus reductant, of members of the thioredoxin superfamily. J Bacteriol 2000;182:723–727.
  • Stewart EJ, Åslund F, Beckwith J. Disulfide bond formation in the Escherichia coli cytoplasm: an in vivo role reversal for the thioredoxins. EMBO J 1998;17:5543–5550.
  • Ortenberg R, Beckwith J. Functions of thiol-disulfide oxidoreductases in E. coli: redox myths, realities, and practicalities. Antioxid Redox Signal 2003;54:403–411.
  • Hudson DA, Gannon SA, Thorpe C. Oxidative protein folding: from thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum. Free Radic Biol Med 2015;80:171–182.
  • Denoncin K, Collet JF. Disulfide bond formation in the bacterial periplasm: major achievements and challenges ahead. Antioxid Redox Signal 2013;19:63–71.
  • Anfinsen CB. Principles that govern the folding of protein chains. Science 1973;181:223–230.
  • Creighton TE. Kinetic study of protein unfolding and refolding using urea gradient electrophoresis. J Mol Biol 1980;137:61–80.
  • Zito E, Melo EP, Yang Y, Wahlander Å, Neubert TA, Ron D. Oxidative protein folding by an endoplasmic reticulum-localized peroxiredoxin. Mol Cell 2010;40:787–797.
  • Tavender TJ, Springate JJ, Bulleid NJ. Recycling of peroxiredoxin IV provides a novel pathway for disulphide formation in the endoplasmic reticulum. EMBO J 2010;29:4185–4197.
  • Zito E, Hansen HG, Yeo GS, Fujii J, Ron D. Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice. Mol Cell 2012;48:39–51.
  • Monteiro G, Horta BB, Pimenta DC, Augusto O, Netto LES. Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C. Proc Natl Acad Sci USA 2007;104:4886–4891.
  • Laurindo FR, Pescatore LA, Fernandes Dde C. Protein disulfide isomerase in redox cell signaling and homeostasis. Free Radic Biol Med 2012;52:1954–1969.
  • Darby NJ, Creighton TE. Characterization of the active site cysteine residues of the thioredoxin-like domains of protein disulfide isomerase. Biochemistry 1995;34:16770–16780.
  • Hudson DA, Thorpe C. Mia40 is a facile oxidant of unfolded reduced proteins but shows minimal isomerase activity. Arch Biochem Biophys 2015;579:1–7.
  • Reed LJ. A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes. J Biol Chem 2001;276:38329–38336.
  • Bunik VI. 2-Oxo acid dehydrogenase complexes in redox regulation. Eur J Biochem 2003;270:1036–1042.
  • Cussiol JR, Alegria TG, Szweda LI, Netto LES. Ohr (organic hydroperoxide resistance protein) possesses a previously undescribed activity, lipoyl-dependent peroxidase. J Biol Chem 2010;285:21943–21950.
  • Si M, Wang J, Xiao X, Guan J, Zhang Y, Ding W, et al. Ohr protects Corynebacterium glutamicum against organic hydroperoxide induced oxidative stress. PLoS One 2015;10:e0131634.
  • Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science 2002;295:1073–1077.
  • Beckwith J. Genetic suppressors and recovery of repressed biochemical memory. J Biol Chem 2009;284:12585–12592.
  • Björnberg O, Ostergaard H, Winther JR. Measuring intracellular redox conditions using GFP-based sensors. Antioxid Redox Signal 2006;8:354–361.
  • Meyer AJ, Dick TP. Fluorescent protein-based redox probes. Antioxid Redox Signal 2010;13:621–650.
  • Østergaard H, Tachibana C, Winther JR. Monitoring disulfide bond formation in the eukaryotic cytosol. J Cell Biol 2004;166:337–345.
  • Morgan B, Ezeriņa D, Amoako TN, Riemer J, Seedorf M, Dick TP. Multiple glutathione disulfide removal pathways mediate cytosolic redox homeostasis. Nat Chem Biol 2013;9:119–125.
  • Schwarzländer M, Dick TP, Meye AJ, Morgan B. Dissecting redox biology using fluorescent protein sensors. Antioxid Redox Signal 2015. [Epub ahead of print]. doi: 10.1089/ars.2015.6266.
  • Imlay JA. The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat Rev Microbiol 2013;11:443–454.
  • Loi VV, Rossius M, Antelmann H. Redox regulation by reversible protein S-thiolation in bacteria. Front Microbiol 2015;6:187.
  • Luebke JL, Giedroc DP. Cysteine sulfur chemistry in transcriptional regulators at the host-bacterial pathogen interface. Biochemistry 2015;54:3235–3249.
  • Green J, Paget MS. Bacterial redox sensors. Nat Rev Microbiol 2004;2:954–966.
  • Antelmann H, Helmann JD. Thiol-based redox switches and gene regulation. Antioxid. Redox Signal 2011;14:1049–1063.
  • Chen PR, Brugarolas P, He C. Redox signaling in human pathogens. Antioxid Redox Signal 2011;14:1107–1118.
  • Vázquez-Torres A. Redox active thiol sensors of oxidative and nitrosative stress. Antioxid Redox Signal 2012;17:1201–1214.
  • Imlay JA. Transcription factors that defend bacteria against reactive oxygen species. Annu Rev Microbiol 2015;69:93–108.
  • Jo I, Chung IY, Bae HW, Kim JS, Song S, Cho YH, Ha NC. Structural details of the OxyR peroxide-sensing mechanism. Proc Natl Acad Sci USA 2015;112:6443–6448.
  • Lee C, Lee SM, Mukhopadhyay P, Kim SJ, Lee SC, Ahn WS, et al. Redox regulation of OxyR requires specific disulfide bond formation involving a rapid kinetic reaction path. Nat Struct Mol Biol 2004;11:1179–1185.
  • Zheng M, Åslund F, Storz G. Activation of the OxyR transcription factor by reversible disulfide bond formation. Science 1998;279:1718–1721.
  • Choi H, Kim S, Mukhopadhyay P, Cho S, Woo J, Storz G, Ryu SE. Structural basis of the redox switch in the OxyR transcription factor. Cell 2001;105:103–113.
  • Tao K. In vivo oxidation-reduction kinetics of OxyR, the transcriptional activator for an oxidative stress-inducible regulon in Escherichia coli. FEBS Lett 1999;457:90–92.
  • Åslund F, Zheng M, Beckwith J, Storz G. Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol-disulfide status. Proc Natl Acad Sci USA 1999;96:6161–6165.
  • Wei Q, Minh PN, Dötsch A, Hildebrand F, Panmanee W, Elfarash A, et al. Global regulation of gene expression by OxyR in an important human opportunistic pathogen. Nucleic Acids Res 2012;40:4320–4333.
  • Kim SO, Merchant K, Nudelman R, Beyer WF, JrKeng T, DeAngelo J, et al. OxyR: a molecular code for redox-related signaling. Cell 2002;109:383–396.
  • Seth D, Hausladen A, Wang YJ, Stamler JS. Endogenous protein S-Nitrosylation in E. coli: regulation by OxyR. Science 2012;336:470–473.
  • Lee JW, Helmann JD. The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation. Nature 2006;440:363–367.
  • Cussiol JRR, Alves SV, Oliveira MA, Netto LES. Organic hydroperoxide resistance gene encodes a thiol-dependent peroxidase. J Biol Chem 2003;278:11570–11578.
  • Dubbs JM, Mongkolsuk S. Peroxide-sensing transcriptional regulators in bacteria. J Bacteriol 2012;194:5495–5503.
  • Panmanee W, Vattanaviboon P, Poole LB, Mongkolsuk S. Novel organic hydroperoxide-sensing and responding mechanisms for OhrR, a major bacterial sensor and regulator of organic hydroperoxide stress. J Bacteriol 2006;188:1389–1395.
  • Fuangthong M, Helmann JD. The OhrR repressor senses organic hydroperoxides by reversible formation of a cysteine-sulfenic acid derivative. Proc Natl Acad Sci USA 2002;99:6690–6695.
  • Lee JW, Soonsanga S, Helmann JD. A complex thiolate switch regulates the Bacillus subtilis organic peroxide sensor OhrR. Proc Natl Acad Sci USA 2007;104:8743–8748.
  • Chi BK, Gronau K, Mäder U, Hessling B, Becher D, Antelmann H. S-bacillithiolation protects against hypochlorite stress in Bacillus subtilis as revealed by transcriptomics and redox proteomics. Mol Cell Proteomics 2011;10:M111.009506.
  • Gaballa A, Chi BK, Roberts AA, Becher D, Hamilton CJ, Antelmann H, Helmann JD. Redox regulation in Bacillus subtilis: the bacilliredoxins BrxA(YphP) and BrxB(YqiW) function in de-bacillithiolation of S-bacillithiolated OhrR and MetE. Antioxid Redox Signal 2014;21:357–367.
  • da Silva Neto JF, Negretto CC, Netto LES. Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin. PLoS One 2012;7:e47090.
  • Kang JG, Paget MS, Seok YJ, Hahn MY, Bae JB, Hahn JS, et al. RsrA, an anti-sigma factor regulated by redox change. EMBO J 1999;18:4292–4298.
  • Jung YG, Cho YB, Kim MS, Yoo JS, Hong SH, Roe JH. Determinants of redox sensitivity in RsrA, a zinc-containing anti-sigma factor for regulating thiol oxidative stress response. Nucleic Acids Res 2011;39:7586–7597.
  • Paget MS, Bae JB, Hahn MY, Li W, Kleanthous C, Roe JH, Buttner MJ. Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch. Mol Microbiol 2001;39:1036–1047.
  • Li W, Bottrill AR, Bibb MJ, Buttner MJ, Paget MS, Kleanthous C. The role of zinc in the disulphide stress-regulated anti-sigma factor RsrA from Streptomyces coelicolor. J Mol Biol 2003;333:461–472.
  • Kim MS, Dufour YS, Yoo JS, Cho YB, Park JH, Nam GB, et al. Conservation of thiol-oxidative stress responses regulated by SigR orthologues in actinomycetes. Mol Microbiol 2012;85:326–344.
  • Park JH, Roe JH. Mycothiol regulates and is regulated by a thiol-specific antisigma factor RsrA and sigma(R) in Streptomyces coelicolor. Mol Microbiol 2008;68:861–870.
  • Nakamura K, Hihara Y. Photon flux density-dependent gene expression in Synechocystis sp. PCC 6803 is regulated by a small, redox-responsive, LuxR-type regulator. J Biol Chem 2006;281:36758–36766.
  • Horiuchi M, Nakamura K, Kojima K, Nishiyama Y, Hatakeyama W, Hisabori T, Hihara Y. The PedR transcriptional regulator interacts with thioredoxin to connect photosynthesis with gene expression in cyanobacteria. Biochem J 2010;431:135–140.
  • Boronat S, Domènech A, Paulo E, Calvo IA, García-Santamarina S, García P, et al. Thiol-based H2O2 signalling in microbial systems. Redox Biol 2014;2:395–399.
  • Izawa S, Maeda K, Sugiyama K, Mano J, Inoue Y, Kimura A. Thioredoxin deficiency causes the constitutive activation of Yap1, an AP-1-like transcription factor in Saccharomyces cerevisiae. J Biol Chem 1999;274:28459–28465.
  • Marinho HS, Real C, Cyrne L, Soares H, Antunes F. Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol 2014;2:535–562.
  • Lee J, Godon C, Lagniel G, Spector D, Garin J, Labarre J, Toledano MB. Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. J Biol Chem 1999;274:16040–16046.
  • Delaunay A, Isnard AD, Toledano MB. H2O2 sensing through oxidation of the Yap1 transcription factor. EMBO J 2000;19:5157–5166.
  • Delaunay A, Pflieger D, Barrault MB, Vinh J, Toledano MB. A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell 2002;111:471–481.
  • Yan C, Lee LH, Davis LI. Crm1p mediates regulated nuclear export of a yeast AP-1-like transcription factor. EMBO J 1998;17:7416–7429.
  • Okazaki S, Tachibana T, Naganuma A, Mano N, Kuge S. Multistep disulfide bond formation in Yap1 is required for sensing and transduction of H2O2 stress signal. Mol Cell 2007;27:675–688.
  • Wood MJ, Storz G, Tjandra N. Structural basis for redox regulation of Yap1 transcription factor localization. Nature 2004;430:917–921.
  • Veal EA, Ross SJ, Malakasi P, Peacock E, Morgan BA. Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1 transcription factor. J Biol Chem 2003;278:30896–30904.
  • Azevedo D, Tacnet F, Delaunay A, Rodrigues-Pousada C, Toledano MB. Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling. Free Radic Biol Med 2003;35:889–900.
  • Fomenko DE, Koc A, Agisheva N, Jacobsen M, Kaya A, Malinouski M, et al. Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide. Proc Natl Acad Sci USA 2011;108:2729–2734.
  • Winterbourn CC, Hampton MB. Thiol chemistry and specificity in redox signaling. Free Radic Biol Med 2008;45:549–561.
  • Day AM, Brown JD, Taylor SR, Rand JD, Morgan BA, Veal EA. Inactivation of a peroxiredoxin by hydrogen peroxide is critical for thioredoxin-mediated repair of oxidized proteins and cell survival. Mol Cell 2012;45:398–408.
  • Matthews JR, Wakasugi N, Virelizier JL, Yodoi J, Hay RT. Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Res 1992;20:3821–3830.
  • Schenk H, Klein M, Erdbrügger W, Dröge W, Schulze-Osthoff K. Distinct effects of thioredoxin and antioxidants on the activation of transcription factors NF-kappa B and AP-1. Proc Natl Acad Sci USA 1994;91:1672–1676.
  • Baldwin AS, Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996;14:649–683.
  • Qin J, Clore GM, Kennedy WM, Huth JR, Gronenborn AM. Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B. Structure 1995;15:289–297.
  • Hirota K, Murata M, Sachi Y, Nakamura H, Takeuchi J, Mori K, Yodoi J. Distinct roles of thioredoxin in the cytoplasm and in the nucleus. A two-step mechanism of redox regulation of transcription factor NF-kappaB. J Biol Chem 1999;274:27891–27897.
  • Curran T, Franza BR Jr. Fos and Jun: the AP-1 connection. Cell 1998;55:395–397.
  • Abate C, Patel L, Rauscher FJ, Curran T. Redox regulation of Fos and Jun DNA-binding activity in vitro. Science 1990;249:1157–1161.
  • Xanthoudakis S, Miao G, Wang F, Pan YC, Curran T. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J 1992;11:3323–3335.
  • Georgiadis MM, Luo M, Gaur RK, Delaplane S, Li X, Kelley MR. Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease. Mutat Res 2008;643:54–63.
  • Kelley MR, Georgiadis MM, Fishel ML. APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Curr Mol Pharmacol 2012;5:36–53.
  • Luo M, Zhang J, He H, Su D, Chen Q, Gross ML, et al. Characterization of the redox activity and disulfide bond formation in apurinic/apyrimidinic endonuclease. Biochemistry 2012;51:695–705.
  • Qin J, Clore GM, Kennedy WP, Kuszewski J, Gronenborn AM. The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal. Structure 1996;15:613–620.
  • Sobotta MC, Liou W, Stöcker S, Talwar D, Oehler M, Ruppert T, et al. Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat Chem Biol 2015;11:64–70.
  • Cao J, Schulte J, Knight A, Leslie NR, Zagozdzon A, Bronson R, et al. Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. EMBO J 2009;28:1505–1517.
  • Jarvis RM, Hughes SM, Ledgerwood EC. Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells. Free Radic Biol Med 2012;53:1522–1530.
  • Yan Y, Sabharwal P, Rao M, Sockanathan S. The antioxidant enzyme Prdx1 controls neuronal differentiation by thiol-redox-dependent activation of GDE2. Cell 2009;138:1209–1221.
  • Flohé L. The impact of thiol peroxidases on redox regulation. Free Radic Res 2015;30:1–17.
  • Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, et al. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 1998;17:2596–2606.
  • Kundumani-Sridharan V, Subramani J, Das KC. Thioredoxin activates MKK4-NFκB pathway in a redox-dependent manner to control manganese superoxide dismutase gene expression in endothelial cells. J Biol Chem 2015;290:17505–17519.

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