Amino Acids

, Volume 41, Issue 1, pp 59–72

Intermolecular disulfide bond to modulate protein function as a redox-sensing switch

Review Article


Recently, redox-regulated biological reactions have been elucidated. In the regulation of these reactions, redox-sensing molecular switches function as unique biological machineries that modulate the functional proteins present in enzymes, transcriptional factors, sensor proteins, and transcriptional factor modulators. The redox-sensing cysteine residues and the disulfide bond formed between these cysteine residues serve as redox-sensing molecular switches; these switches sense cellular oxidizing factors such as oxygen, reactive oxygen species, and cellular reducing factors such as thioredoxin (Trx), glutathione (GSH), and their family molecules. Depending on the redox status, the switch directly modulates the protein function via the “locking and unlocking” of the critically functional residue or indirectly modulates the protein function via “protein conformational changes,” which affects the functioning of a distantly located critical residue in an allostery-like fashion or a topology change. Redox-sensing switches can be classified into two types—intramolecular (intrasubunit) and intermolecular (intersubunit) ones. Further, depending on the sensing specificity to reducing factors, the switch subtype is classified into Trx, GSH, or their family molecules-specific type. This review focused on the intermolecular redox-sensing switches found in various proteins.


Disulfide bond Glutathione Redox-sensitive cysteine Redox-sensing switch Thioredoxin 


  1. Alonso A, Sasin J, Bottini N, Friedberg I, Friedberg I, Osterman A, Godzik A, Hunter T, Dixon J, Mustelin T (2004) Protein tyrosine phosphatases in the human genome. Cell 117:699–711PubMedCrossRefGoogle Scholar
  2. Aravind L, Anantharaman V, Balaji S, Babu MM, Iyer LM (2005) The many faces of the helix-turn-helix domain: transcription regulation and beyond. FEMS Microbiol Rev 29:231–262PubMedGoogle Scholar
  3. Barford D, Jia Z, Tonks NK (1995) Protein tyrosine phosphatases take off. Nat Srtuct Biol 2:1043–1053CrossRefGoogle Scholar
  4. Bass RB, Butler SL, Chervitz SA, Gloor SLS, Falke JJ (2007) Use of site directed cysteine and disulfide chemistry to probe protein structure and dynamics: applications to soluble and transmembrane receptors of bacterial chemotaxis. Method Enzymol 423:25–51CrossRefGoogle Scholar
  5. Biswas S, Chida AS, Rahman I (2006) Redox modifications of protein-thiols: emerging roles in cell signaling. Biochem Pharmacol 71:551–564PubMedCrossRefGoogle Scholar
  6. Brennan JP, Wait R, Begum S, Bell JR, Dunn MJ, Eaton P (2004) Detection and mapping of widespread intermolecular protein disulfide formation during cardiac oxidative stress using proteomics with diagonal electrophoresis. J Biol Chem 279:41352–41360PubMedCrossRefGoogle Scholar
  7. Brennan JP, Bardswell SC, Burgoyne JR, Fuller W, Schröder E, Wait R, Begum S, Kentish JC, Eaton P (2006) Oxidant-induced activation of type I protein kinase a is mediated by RI subunit interprotein disulfide bond formation. J Biol Chem 281:21827–21836PubMedCrossRefGoogle Scholar
  8. Brenner S, Elgar G, Sandford R, Macrae A, Venkatesh B, Aparicio S (1993) Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome. Nature 366:265–268PubMedCrossRefGoogle Scholar
  9. Canfield DE (2005) The early history of atmospheric oxygen. Annu Rev Earth Planet Sci 33:1–36CrossRefGoogle Scholar
  10. Casagrande S, Bonetto V, Fratellim M, Gianazza E, Eberini I, Massignan T, Salmona M, Chang G, Holmgren A, Ghezzi P (2002) Glutathionylation of human thioredoxin: a possible crosstalk between the glutathione and thioredoxin systems. Proc Natl Acad Sci USA 99:9745–9749PubMedCrossRefGoogle Scholar
  11. Clancy CJ, Gilbert HF (1987) Thiol/disulfide exchange in the thioredoxin-catalyzed reductive activation of spinach chloroplast fructose-1, 6-bisphosphatase. Kinetics and thermodynamics. J Biol Chem 262:13545–13549Google Scholar
  12. Crétin C, Luchetta P, Joly C, Decottignies P, Lepiniec L, Gadal P, Sallantin M, Huet JC, Pernollet JC (1990) Primary structure of sorghum malate dehydrogenase (NADP) deduced from cDNA sequence. Homology with malate dehydrogenase (NAD). Eur J Biochem 192:299–303PubMedCrossRefGoogle Scholar
  13. Cumming RC, Andon NL, Haynes PA, Park M, Fischer WH, Schubert D (2004) Protein disulfide bond formation in the cytoplasm during oxidative stress. J Biol Chem 279:21749–21758PubMedCrossRefGoogle Scholar
  14. Cussiol JR, Alves SV, de Oliveira MA, Netto LE (2003) Organic hydroperoxide resistance gene encodes a thiol-dependent peroxidase. J Biol Chem 278:11570–11578PubMedCrossRefGoogle Scholar
  15. de Piña MZ, Vázquez-Meza H, Pardo JP, Rendón JL, Villalobos-Molina R, Rivers-Rosas H, Piña E (2008) Signaling the signal, cyclic AMP-dependent protein kinase inhibition by insulin-formed H2O2 and reactivation by thioredoxin. J Biol Chem 283:12373–12386PubMedCrossRefGoogle Scholar
  16. Delaunay A, Isnard A-D, Toledano MB (2000) H2O2 sensing through oxidation of the Yap1 transcription factor. EMBO J 19:5157–5166PubMedCrossRefGoogle Scholar
  17. Delaunay A, Pflieger D, Barrault MB, Vinh J, Toledano MB (2002) A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell 111:471–481PubMedCrossRefGoogle Scholar
  18. First EA, Bubis J, Taylor SS (1988) Subunit interaction sites between the regulatory and catalytic subunits of cAMP-dependent protein kinase. Identification of a specific interchain disulfide bond. J Biol Chem 263:5176–5182PubMedGoogle Scholar
  19. Fuangthong M, Helmann JD (2002) The OhrR repressor senses organic hydroperoxides by reversible formation of a cysteine-sulfenic acid derivative. Proc Natl Acad Sci USA 99:6690–6695PubMedCrossRefGoogle Scholar
  20. Gietl C (1992) Malate dehydrogenase isoenzymes: cellular locations and role in the flow of metabolites between the cytoplasm and cell organelles. Biochim Biophys Acta 1100:217–234PubMedCrossRefGoogle Scholar
  21. Giusn D, Botero A, Shah S, Curry HA (1999) Intracellular oxidation/reduction status in the regulation of transcription factors NF-κB and AP-1. Toxicol Lett 106:93–106CrossRefGoogle Scholar
  22. Gupta N, Ragsdale SW (2008) Dual roles of an essential cysteine residue in activity of a redox-regulated bacterial transcriptional activator. J Biol Chem 283:28721–29828PubMedCrossRefGoogle Scholar
  23. Hara S, Motohashi K, Arisaka F, Romano PG, Hosoya-Matsuda N, Kikuchi N, Fusada N, Hisabori T (2006) Thioredoxin-h1 reduces and reactivates the oxidized cytosolic malate dehydrogenase dimer in higher plants. J Biol Chem 281:32065–32071PubMedCrossRefGoogle Scholar
  24. Hawkins HC, Blackburn EC, Freedman RB (1991) Comparison of the activities of protein disulphide-isomerase and thioredoxin in catalyzing disulphide isomerization in a protein substrate. Biochem J 275:349–353PubMedGoogle Scholar
  25. Herscovitch M, Comb W, Ennis T, Coleman K, Yong S, Armstead B, Kalaitzidis D, Chandani S, Gilmore TD (2008) Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347. Biochem Biophys Res Commun 367:103–108PubMedCrossRefGoogle Scholar
  26. Hock B, Gietl C (1982) Cell-free synthesis of watermelon glyoxysomal malate dehydrogenase: a comparison with the mitochondrial isoenzyme. Ann N Y Acad Sci 386:350–376PubMedCrossRefGoogle Scholar
  27. Hofmann B, Hecht HJ, Flohé L (2002) Peroxiredoxins. Biol Chem 383:347–364PubMedCrossRefGoogle Scholar
  28. Holmgren A (1979) Thioredoxin catalyzes the reduction of insulin disulfides by dithiothreitol and dihydrolipoamide. J Biol Chem 254:9627–9632PubMedGoogle Scholar
  29. Horowitz PM, Criscimagna NL (1988) Sulfhydryl-directed triggering of conformational changes in the enzyme rhodanese. J Biol Chem 263:10278–10283PubMedGoogle Scholar
  30. Humphries KM, Juliano C, Taylor SS (2002) Regulation of cAMP-dependent protein kinase activity by glutathionylation. J Biol Chem 277:43505–43511PubMedCrossRefGoogle Scholar
  31. Humphries KM, Deal MS, Taylor SS (2005) Enhanced dephosphorylation of cAMP-dependent protein kinase by oxidation and thiol modification. J Biol Chem 280:2750–2758PubMedCrossRefGoogle Scholar
  32. Joyce MG, Levy C, Gabor K, Pop SM, Biehl BD, Doukov TI, Ryter JM, Mazon H, Smidt H, van den Heuvel RHH, Ragsdale SW, van der Oost J, Leys D (2006) CprK crystal structures reveal mechanism for transcriptional control of halorespiration. J Biol Chem 281:28318–28325PubMedCrossRefGoogle Scholar
  33. Kasting JF, Siefert JL (2002) Life and the evolution of Earth’s atmosphere. Science 296:1066–1068PubMedCrossRefGoogle Scholar
  34. Lassing I, Schmitzberger F, Björnstedt M, Holmgren A, Nordlund P, Schutt CE, Lindberg U (2007) Molecular and structural basis for redox regulation of beta-actin. J Mol Biol 370:331–348PubMedCrossRefGoogle Scholar
  35. Lee JW, Soonsanga S, Helmann JD (2007) A complex thiolate switch regulates the Bacillus subtilis organic peroxide sensor OhrR. Proc Natl Acad Sci USA 104:8743–8748PubMedCrossRefGoogle Scholar
  36. Linke K, Jakob U (2003) Not every disulfide lasts forever: disulfide bond formation as a redox switch. Antioxid Redox Signal 5:425–434PubMedCrossRefGoogle Scholar
  37. Lugo-Mas P, Dey A, Xu L, Davin SD, Benedict J, Kaminsky W, Hodgson KO, Hedman B, Solomon EI, Kovacs JA (2006) How does single oxygen atom addition affect the properties of an Fe-nitrile hydratase analogue? The compensatory role of the unmodified thiolate. J Am Chem Soc 128:11211–11221PubMedCrossRefGoogle Scholar
  38. Lundstrom J, Holmgren A (1990) Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity. J Biol Chem 265:9114–9120PubMedGoogle Scholar
  39. Matsumura T, Okamoto K, Iwahara S, Hori H, Takahashi Y, Nishino T, Abe Y (2008) Dimer-oligomer interconversion of wild-type and mutant rat 2-Cys peroxiredoxin: disulfide formation at dimer-dimer interfaces is not essential for decamerization. J Biol Chem 283:284–293PubMedCrossRefGoogle Scholar
  40. Mikkelsen R, Mutenda KE, Mant A, Schurmann P, Blennow A (2005) Alpha-glucan, water dikinase (GWD): a plastidic enzyme with redox-regulated and coordinated catalytic activity and binding affinity. Proc Natl Acad Sci USA 102:1785–1790PubMedCrossRefGoogle Scholar
  41. Millar AH, Wiskich JT, Whelan J, Day DA (1993) Organic acid activation of the alternative oxidase of plant mitochondria. FEBS Lett 329:259–262PubMedCrossRefGoogle Scholar
  42. Musso R, Di Lauro R, Rosenberg M, de Crombrugghe B (1977) Nucleotide sequence of the operator-promoter region of the galactose operon of Escherichia coli. Proc Natl Acad Sci USA 74:106–110PubMedCrossRefGoogle Scholar
  43. Nagahara N (2007) Molecular evolution of thioredoxin-dependent redox-sensing switch in mercaptopyruvate sulfurtransferase. In: Mohan RM (ed) Research advances in biological chemistry. Global Research Network, Kerala, pp 19–26Google Scholar
  44. Nagahara N, Katayama A (2005) Post-translational regulation of mercaptopyruvate sulfurtransferase via a low redox potential cysteine-sulfenate in the maintenance of redox homeostasis. J Biol Chem 280:34569–34576PubMedCrossRefGoogle Scholar
  45. Nagahara N, Nishino T (1996) Role of amino acid residues in the active site of rat liver mercaptopyruvate sulfurtransferase. cDNA cloning overexpression, and site-directed mutagenesis. J Biol Chem 271:27395–27401PubMedCrossRefGoogle Scholar
  46. Nagahara N, Sawada N (2006) The mercaptopyruvate pathway in cysteine catabolism: a physiologic role and related disease of the multifunctional 3-mercaptopyruvate sulfurtransferase. Curr Med Chem 13:1219–1230PubMedCrossRefGoogle Scholar
  47. Nagahara N, Okazaki T, Nishino T (1995) Cytosolic mercaptopyruvate sulfurtransferase is evolutionarily related to mitochondrial rhodanese. Striking similarity in active site amino acid sequence and the increase in the mercaptopyruvate sulfurtransferase activity of rhodanese by site-directed mutagenesis. J Biol Chem 270:16230–16235PubMedCrossRefGoogle Scholar
  48. Nagahara N, Ito T, Kitamura H, Nishino T (1998) Tissue and subcellular distribution of mercaptopyruvate sulfurtransferase in the rat: confocal laser fluorescence and immunoelectron microscopic studies combined with biochemical analysis. Histochem Cell Biol 110:243–250PubMedCrossRefGoogle Scholar
  49. Nagahara N, Ito T, Minami M (1999) Mercaptopyruvate sulfurtransferase as a defense against cyanide toxication: molecular properties and mode of detoxification. Histol Histopathol 14:1277–12286PubMedGoogle Scholar
  50. Nagahara N, Sreeja VG, Li Q, Shimizu T, Tsuchiya T, Fujii-Kuriyama YA (2004) Point mutation in a silencer element markedly reduces promoter activity of the human mercaptopyruvate sulfurtransferase gene. Biochim Biophys Acta 1680:176–184PubMedGoogle Scholar
  51. Nagahara N, Yoshii T, Abe Y, Matsumura T (2007) Thioredoxin-dependent enzymatic activation of mercaptopyruvate sulfurtransferase. An intersubunit disulfide bond serves as a redox switch for activation. J Biol Chem 282:1561–1569PubMedCrossRefGoogle Scholar
  52. Nagahara N, Matsumura T, Okamoto R, Kajihara K (2009a) Protein cysteine modifications: (1) Medical chemistry for proteomics. Curr Med Chem 16:4419–4444Google Scholar
  53. Nagahara N, Matsumura T, Okamoto R, Kajihara K (2009b) Protein cysteine modifications: (2) Reactivity specificity and topics of medical chemistry and protein engineering. Curr Med Chem 16:4490–4501Google Scholar
  54. Nakamura T, Yamaguchi Y, Sano H (2000) Plant mercaptopyruvate sulfurtransferases: molecular cloning, subcellular localization and enzymatic activities. Eur J Biochem 267:5621–5630PubMedCrossRefGoogle Scholar
  55. Nelson NC, Taylor SS (1983) Selective protection of sulfhydryl groups in cAMP-dependent protein kinase II. J Biol Chem 258:10981–10987PubMedGoogle Scholar
  56. Ohlrogge J, Browse J (1995) Lipid biosynthesis. Plant Cell 7:957–970PubMedCrossRefGoogle Scholar
  57. Oudot C, Jaquinod M, Cortay JC, Cozzone AJ, Jault JM (1999) The isocitrate dehydrogenase kinase/phosphatase from Escherichia coli is highly sensitive to in vitro oxidative conditions role of cysteine67 and cysteine108 in the formation of a disulfide-bonded homodimer. Eur J Biochem 262:224–229PubMedCrossRefGoogle Scholar
  58. Panmanee W, Vattanaviboon P, Poole LB, Mongkolsuk S (2006) Novel organic hydroperoxide-sensing and responding mechanisms for OhrR, a major bacterial sensor and regulator of organic hydroperoxide stress. J Bacteriol 188:1389–1395PubMedCrossRefGoogle Scholar
  59. Park EM, Thomas JA (1989) Reduction of protein mixed disulfides (dethiolation) by Escherichia coli thioredoxin: a study with glycogen phosphorylase b and creatine kinase. Arch Biochem Biophys 272:25–31PubMedCrossRefGoogle Scholar
  60. Poole LB, Karplus PA, Claiborne A (1989) The non-flavin redox center of the streptococcal NADH peroxidase. II. Evidence for a stabilized cysteine-sulfenic acid. J Biol Chem 264:12330–12338PubMedGoogle Scholar
  61. Pop SM, Kolarik RJ, Ragsdale SW (2004) Regulation of anaerobic dehalorespiration by the transcriptional activator CprK. J Biol Chem 279:49910–49918PubMedCrossRefGoogle Scholar
  62. Powis G, Montfort WR (2001) Properties and biological activities of thioredoxins. Annu Rev Pharmacol Toxicol 41:261–295PubMedCrossRefGoogle Scholar
  63. Raynaud F, Evain-Brion D, Gerbaud P, Marciano D, Gorin I, Liapi C, Anderson WB (1997) Oxidative modulation of cyclic AMP-dependent protein kinase in human fibroblasts: possible role in psoriasis. Free Radic Biol Med 22:623–632PubMedCrossRefGoogle Scholar
  64. Rhoads DM, Umbach AL, Sweet CR, Lennon AM, Rauch GS, Siedow JN (1998) Regulation of the cyanide-resistant alternative oxidase of plant mitochondria. Identification of the cysteine residue involved in alpha-keto acid stimulation and intersubunit disulfide bond formation. J Biol Chem 273:30750–30756PubMedCrossRefGoogle Scholar
  65. Ribas-Carbo M, Lennon AM, Robinson SA, Giles L, Berry JA, Siedow JN (1997) The regulation of electron partitioning between the cytochrome and alternative pathways in soybean cotyledon and root mitochondria. Plant Physiol 113:903–911PubMedGoogle Scholar
  66. Rittinger K, Negre D, Divita G, Scarabel M, Bonod-Bidaud C, Goody RS, Cozzone AJ, Cortay JC (1996) Escherichia coli isocitrate dehydrogenase kinase/phosphatase. Overproduction and kinetics of interaction with its substrates by using intrinsic fluorescence and fluorescent nucleotide analogues. Eur J Biochem 237:247–254PubMedCrossRefGoogle Scholar
  67. Salmeen A, Andersen JN, Myers MP, Meng TC, Hinks JA, Tonks NK, Barford D (2003) Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature 423:769–773PubMedCrossRefGoogle Scholar
  68. Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G (2001) Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme. Proc Natl Acad Sci USA 98:9533–9538PubMedCrossRefGoogle Scholar
  69. Sasaki Y, Konishi T, Nagano Y (1995) The compartmentation of acetyl-coenzyme A carboxylase in plants. Plant Physiol 108:445–449PubMedGoogle Scholar
  70. Sasaki Y, Kozaki A, Ohmori A, Iguchi H, Nagano Y (2001) Chloroplast RNA editing required for functional acetyl-CoA carboxylase in plants. J Biol Chem 276:3937–3940Google Scholar
  71. Scheibe R, Kampfenkel K, Wessels R, Tripier D (1991) Primary structure and analysis of the location of the regulatory disulfide bond of pea chloroplast NADP-malate dehydrogenase. Biochem Biophys Acta 1076:1–8PubMedCrossRefGoogle Scholar
  72. Sebban H, Yamaoka S, Courtois G (2006) Posttranslational modifications of NEMO and its partners in NF-κB signaling. Trends Cell Biol 16:569–577PubMedCrossRefGoogle Scholar
  73. Sevier CS, Kaiser CA (2006) Disulfide transfer between two conserved cysteine pairs imparts selectivity to protein oxidation by Ero1. Mol Biol Cell 17:2256–2266PubMedCrossRefGoogle Scholar
  74. Siedow JN, Umbach A (1995) Plant mitochondrial electron transfer and molecular biology. Plant Cell 7:821–831PubMedCrossRefGoogle Scholar
  75. Smidt H, de Vos WM (2004) Anaerobic microbial dehalogenation. Annu Rev Microbiol 58:43–73PubMedCrossRefGoogle Scholar
  76. Sohn J, Rudolph J (2003) Catalytic and chemical competence of regulation of cdc25 phosphatase by oxidation/reduction. Biochemistry 42:10060–10070PubMedCrossRefGoogle Scholar
  77. Song H, Bao S, Ramanadham S, Turk J (2006) Effects of biological oxidants on the catalytic activity and structure of group VIA phospholipase A2. Biochemistry 45:6392–6406PubMedCrossRefGoogle Scholar
  78. Sukchawalit R, Loprasert S, Atichartpongkul S, Mongkolsuk S (2001) Complex regulation of the organic hydroperoxide resistance gene (ohr) from Xanthomonas involves OhrR, a novel organic peroxide-inducible negative regulator, and posttranscriptional modifications. J Bacteriol 183:4405–4412PubMedCrossRefGoogle Scholar
  79. Swem LR, Kraft BJ, Swem DL, Setterdahl AT, Masuda S, Knaff DB, Zaleski JM, Bauer CE (2003) Signal transduction by the global regulator RegB is mediated by a redox-active cysteine. EMBO J 22:4699–4708PubMedCrossRefGoogle Scholar
  80. Swem LR, Swem DL, Wu J, Bauer CE (2007) Purification and assays of Rhodobacter capsulatus RegB-RegA two-component signal transduction system. Methods Enzymol 422:171–183PubMedCrossRefGoogle Scholar
  81. Takio K, Smith SB, Krebs EG, Walsh KA, Titani K (1982) Primary structure of the regulatory subunit of type II cAMP-dependent protein kinase from bovine cardiac muscle. Proc Natl Acad Sci USA 79:2544–2548PubMedCrossRefGoogle Scholar
  82. Taylor SS, Yang J, Wu J, Haste NM, Radzio-Andzelm E, Anand G (2004) PKA: a portrait of protein kinase dynamics. Biochim Biophys Acta 1697:259–269PubMedGoogle Scholar
  83. Taylor SS, Kim C, Vigil D, Haste NM, Yang J, Wu J, Anand GS (2005) Dynamics of signaling by PKA. Biochim Biophys Acta 1754:25–37PubMedGoogle Scholar
  84. Umbach AL, Siedow JN (1993) Covalent and noncovalent dimers of the cyanide-resistant alternative oxidase protein in higher plant mitochondria and their relationship to enzyme activity. Plant Physiol 103:845–854PubMedGoogle Scholar
  85. Umbach AL, Siedow JN (1996) The reaction of the soybean cotyledon mitochondrial cyanide-resistant oxidase with sulfhydryl reagents suggests that alpha-keto acid activation involves the formation of a thiohemiacetal. J Biol Chem 271:25019–25026PubMedCrossRefGoogle Scholar
  86. Umbach AL, Wiskich JT, Siedow JN (1994) Regulation of alternative oxidase kinetics by pyruvate and intermolecular disulfide bond redox status in soybean seedling mitochondria. FEBS Lett 348:181–184PubMedCrossRefGoogle Scholar
  87. Utkin I, Woese C, Wiegel J (1994) Isolation and characterization of Desulfitobacterium dehalogenans gen. nov., sp. nov., an anaerobic bacterium which reductively dechlorinates chlorophenolic compounds. Int J Syst Bacteriol 44:612–619PubMedCrossRefGoogle Scholar
  88. van der Wijk T, Overvoorde J, den Hertog J (2004) H2O2-induced intermolecular disulfide bond formation between receptor protein-tyrosine phosphatases. J Biol Chem 279:44355–44361PubMedCrossRefGoogle Scholar
  89. van Montfort RL, Congreve M, Tisi D, Carr R, Jhoti H (2003) Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature 423:773–777PubMedCrossRefGoogle Scholar
  90. Vanlerberghe GC, McIntosh L (1997) Alternative oxidase: from gene to function. Annu Rev Plant Physiol Plant Mol Biol 48:703–734PubMedCrossRefGoogle Scholar
  91. Vanlerberghe GC, Day DA, Wiskich JT, Vanlerberghe AE, McIntosh L (1995) Alternative oxidase activity in tobacco leaf mitochondria (dependence on tricarboxylic acid cycle-mediated redox regulation and pyruvate activation). Plant Physiol 109:353–361PubMedGoogle Scholar
  92. Waksman G, Krishna TS, Williams CH Jr, Kuriyan J (1994) Crystal structure of Escherichia coli thioredoxin reductase refined at 2 Å resolution. Implications for a large conformational change during catalysis. J Mol Biol 236:800–816PubMedCrossRefGoogle Scholar
  93. Walk RA, Hock B (1978) Cell-free synthesis of glyoxysomal malate dehydrogenase. Biochem Biophys Res Commun 81:636–643PubMedCrossRefGoogle Scholar
  94. Wang Y, De Keulenaer GW, Lee RT (2002) Vitamin D3-up-regulated protein-1 is a stress-responsive gene that regulates cardiomyocyte viability through interaction with thioredoxin. J Biol Chem 277:26496–26500PubMedCrossRefGoogle Scholar
  95. Wiegel J, Wu QZ (2000) Microbial reductive dehalogenation of polychlorinated biphenyls. FEMS Microbiol Ecol 32:1–15PubMedCrossRefGoogle Scholar
  96. Wiegel J, Zhang X, Wu Q (1999) Anaerobic dehalogenation of hydroxylated polychlorinated biphenyls by Desulfitobacterium dehalogenans. Appl Environ Microbiol 65:2217–2221PubMedGoogle Scholar
  97. Winstead MV, Balsinde J, Dennis EA (2000) Calcium-independent phospholipase A2: structure and function. Biochim Biophys Acta 1488:28–39PubMedGoogle Scholar
  98. Yamamoto Y, Kim DW, Kwak YT, Prajapti S, Verma U, Gaynor RB (2001) IKKγ/NEMO facilitates the recruitment of the IκBα proteins into the IκB kinase complex. J Biol Chem 276:36327–36336PubMedCrossRefGoogle Scholar
  99. Yamazaki D, Motohashi K, Kasama T, Hara Y, Hisabori T (2004) Target proteins of the cytosolic thioredoxins in Arabidopsis thaliana. Plant Cell Physiol 45:18–27PubMedCrossRefGoogle Scholar
  100. Zheng M, Aslund F, Storz G (1998) Activation of the OxyR transcription factor by reversible disulfide bond formation. Science 279:1718–1721PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Environmental MedicineNippon Medical SchoolTokyoJapan

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