The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Dithiol     4-methylbenzene-1,2-dithiol

Synonyms: SureCN331198, NSC-5391, ACMC-1AHIT, AG-F-66236, ANW-30822, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of o-Toluenesulfonylamide

  • DsbB is an E. coli membrane protein that oxidizes DsbA, a periplasmic dithiol oxidase [1].
  • Exogenous recombinant human thioredoxin (rTRX, > or = 500 nM), a dithiol reductase enzyme, inhibited the expression of human immunodeficiency virus (HIV) 1BaL in human macrophages (M phi) by 71% (range, 26-100%), as evaluated by p24 antigen production and the integration of provirus at 14 d after infection [2].
  • Mechanisms by which the dithiol chelating agent 2, 3-dimercaptopropane-1-sulfonate (DMPS) significantly alters the renal tubular transport, accumulation, and toxicity of inorganic mercury were studied in isolated perfused pars recta (S2) segments of proximal tubules of rabbits [3].
  • Oxidation-reduction titrations for the active-site disulfide/dithiol couples of the helX- and ccl2-encoded proteins involved in cytochrome c biogenesis in the purple non-sulfur bacterium Rhodobacter capsulatus have been carried out [4].
  • The high stability of the soluble Thermus thermophilus Rieske protein permits chemical reduction of the disulfide bond and characterization of the sulfhydryl (dithiol) form by protein-film voltammetry [5].

High impact information on o-Toluenesulfonylamide


Chemical compound and disease context of o-Toluenesulfonylamide


Biological context of o-Toluenesulfonylamide

  • The dithiol chelator, Cd2+, and the thiol oxidant, copper o-phenanthroline, produced discharge of the membrane potential when added at the steady state and inhibited its establishment when added prior to energization by ATP [16].
  • Monobromobimane, which inhibits mitochondrial membrane depolarization by preventing dithiol cross-linking, inhibited depolarization and apoptosis in 4G5 cells [17].
  • The ubiquitous glutaredoxin protein family is present in both prokaryotes and eukaryotes, and is closely related to the thioredoxins, which reduce their substrates using a dithiol mechanism as part of the cellular defense against oxidative stress [18].
  • The proteins altered at the C terminus were still dithiol-dependent for full activation, with activation kinetics similar to those of the wild type enzyme [19].
  • Vicinal dithiol-binding agent, phenylarsine oxide, inhibits inducible nitric-oxide synthase gene expression at a step of nuclear factor-kappaB DNA binding in hepatocytes [20].

Anatomical context of o-Toluenesulfonylamide

  • The biological significance of the generation of a redox potential in lymphocyte activation, and the possible involvement of dithiol reduction in the induction of IL-2R/Tac are discussed [21].
  • Evidence for a dithiol-activated signaling pathway in natural killer cell avidity regulation of leukocyte function antigen-1: structural requirements and relationship to phorbol ester- and CD16-triggered pathways [22].
  • At high concentrations, gliotoxin was metabolized by hepatocytes to a reduced (dithiol) metabolite and glutathione was rapidly oxidized [23].
  • These data suggest (i) that the dithiol cysteines are not oxidized by photodynamic action, but rather became inaccessible to oxidants; and (ii) that irradiation of hematoporphyrin-loaded mitochondria does not lead to pore denaturation, but rather to site-selective inactivation of discrete pore functional domains [24].
  • DsbB is an Escherichia coli plasma membrane protein that reoxidizes the Cys30-Pro-His-Cys33 active site of DsbA, the primary dithiol oxidant in the periplasm [25].

Associations of o-Toluenesulfonylamide with other chemical compounds

  • Thioredoxin was 1000-fold more efficient on a molar basis than the model dithiol, dithiothreitol, in reactivating reduced, denatured RNase, suggesting that thioredoxin acts as an efficient catalyst for disulfide interchange [26].
  • This rate is orders of magnitude faster than the reaction of dithiol Trx with insulin disulfides [27].
  • Free FAD is not required for the catalysis of dithiol oxidation by Ero1p, but it is sufficient to drive disulfide bond formation under anaerobic conditions [28].
  • Characterization of recombinant mutant rat TrxR with SeCys(498) replaced by Cys having a 100-fold lower k(cat) for Trx reduction revealed the C-terminal redox center was present as a dithiol when the Cys(59)-Cys(64) was a disulfide, demonstrating that the selenium atom with its larger radius is critical for formation of the unique selenenylsulfide [29].
  • T. brucei thioredoxin contains a third cysteine (Cys(68)) in addition to the redox active dithiol/disulfide [30].

Gene context of o-Toluenesulfonylamide


Analytical, diagnostic and therapeutic context of o-Toluenesulfonylamide

  • Residues surrounding the tetracysteine motif were randomized and fused to GFP, retrovirally transduced into mammalian cells and iteratively sorted by fluorescence-activated cell sorting for high FRET from GFP to ReAsH in the presence of increasing concentrations of dithiol competitors [36].
  • Iodophenylarsine oxide and arsenical affinity chromatography: new probes for dithiol proteins. Application to tubulins and to components of the insulin receptor-glucose transporter signal transduction pathway [37].
  • MALDI experiments suggest that disulfide formation on glutathionylation is accompanied by significant structural changes, in contrast with dithiol thioredoxins and glutaredoxins, where differences between oxidized and reduced forms are subtle and local [18].
  • Incubation of the dithiol derivative of these compounds with DNA and Fe3+ is sufficient to cause single- and double-stranded breaks as determined by neutral agarose gel electrophoresis [38].
  • Titrations of the disulfide/dithiol couple of a peptide designed to serve as a model for R. capsulatus apocytochrome c(2) have also been carried out, and an E(m) value of -170 +/- 10 mV was measured for the model peptide at pH 7 [4].


  1. Crystal Structure of the DsbB-DsbA Complex Reveals a Mechanism of Disulfide Bond Generation. Inaba, K., Murakami, S., Suzuki, M., Nakagawa, A., Yamashita, E., Okada, K., Ito, K. Cell (2006) [Pubmed]
  2. Opposing regulatory effects of thioredoxin and eosinophil cytotoxicity-enhancing factor on the development of human immunodeficiency virus 1. Newman, G.W., Balcewicz-Sablinska, M.K., Guarnaccia, J.R., Remold, H.G., Silberstein, D.S. J. Exp. Med. (1994) [Pubmed]
  3. Mechanisms of action of 2,3-dimercaptopropane-1-sulfonate and the transport, disposition, and toxicity of inorganic mercury in isolated perfused segments of rabbit proximal tubules. Zalups, R.K., Parks, L.D., Cannon, V.T., Barfuss, D.W. Mol. Pharmacol. (1998) [Pubmed]
  4. Oxidation-reduction properties of disulfide-containing proteins of the Rhodobacter capsulatus cytochrome c biogenesis system. Setterdahl, A.T., Goldman, B.S., Hirasawa, M., Jacquot, P., Smith, A.J., Kranz, R.G., Knaff, D.B. Biochemistry (2000) [Pubmed]
  5. Breaking and re-forming the disulfide bond at the high-potential, respiratory-type Rieske [2Fe-2S] center of thermus thermophilus: characterization of the sulfhydryl state by protein-film voltammetry. Zu, Y., Fee, J.A., Hirst, J. Biochemistry (2002) [Pubmed]
  6. Redox regulation of cellular activation. Nakamura, H., Nakamura, K., Yodoi, J. Annu. Rev. Immunol. (1997) [Pubmed]
  7. Twists in catalysis: alternating conformations of Escherichia coli thioredoxin reductase. Lennon, B.W., Williams, C.H., Ludwig, M.L. Science (2000) [Pubmed]
  8. A genetic tool used to identify thioredoxin as a mediator of a growth inhibitory signal. Deiss, L.P., Kimchi, A. Science (1991) [Pubmed]
  9. 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. Jonda, S., Huber-Wunderlich, M., Glockshuber, R., Mössner, E. EMBO J. (1999) [Pubmed]
  10. Identification and characterization of a new disulfide isomerase-like protein (DsbD) in Escherichia coli. Missiakas, D., Schwager, F., Raina, S. EMBO J. (1995) [Pubmed]
  11. Replacement of Trp28 in Escherichia coli thioredoxin by site-directed mutagenesis affects thermodynamic stability but not function. Slaby, I., Cerna, V., Jeng, M.F., Dyson, H.J., Holmgren, A. J. Biol. Chem. (1996) [Pubmed]
  12. Thiol-mediated disassembly and reassembly of [2Fe-2S] clusters in the redox-regulated transcription factor SoxR. Ding, H., Demple, B. Biochemistry (1998) [Pubmed]
  13. Evidence for a role of a vicinal dithiol in the transport of gamma-butyrobetaine in Agrobacterium sp. Nobile, S., Deshusses, J. Biochimie (1988) [Pubmed]
  14. The primary structure of Escherichia coli glutaredoxin. Distant homology with thioredoxins in a superfamily of small proteins with a redox-active cystine disulfide/cysteine dithiol. Höög, J.O., Jörnvall, H., Holmgren, A., Carlquist, M., Persson, M. Eur. J. Biochem. (1983) [Pubmed]
  15. Arsenical-based affinity chromatography of vicinal dithiol-containing proteins: purification of L1210 leukemia cytoplasmic proteins and the recombinant rat c-erb A beta 1 T3 receptor. Kalef, E., Walfish, P.G., Gitler, C. Anal. Biochem. (1993) [Pubmed]
  16. Evidence for the involvement of coupling factor B in the H+ channel of the mitochondrial H+-ATPase. Sanadi, D.R., Pringle, M., Kantham, L., Hughes, J.B., Srivastava, A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  17. Mitochondrial membrane sensitivity to depolarization in acute myeloblastic leukemia is associated with spontaneous in vitro apoptosis, wild-type TP53, and vicinal thiol/disulfide status. Pallis, M., Grundy, M., Turzanski, J., Kofler, R., Russell, N. Blood (2001) [Pubmed]
  18. Molecular mapping of functionalities in the solution structure of reduced Grx4, a monothiol glutaredoxin from Escherichia coli. Fladvad, M., Bellanda, M., Fernandes, A.P., Mammi, S., Vlamis-Gardikas, A., Holmgren, A., Sunnerhagen, M. J. Biol. Chem. (2005) [Pubmed]
  19. Identification and characterization of the second regulatory disulfide bridge of recombinant sorghum leaf NADP-malate dehydrogenase. Issakidis, E., Saarinen, M., Decottignies, P., Jacquot, J.P., Crétin, C., Gadal, P., Miginiac-Maslow, M. J. Biol. Chem. (1994) [Pubmed]
  20. Vicinal dithiol-binding agent, phenylarsine oxide, inhibits inducible nitric-oxide synthase gene expression at a step of nuclear factor-kappaB DNA binding in hepatocytes. Oda, M., Sakitani, K., Kaibori, M., Inoue, T., Kamiyama, Y., Okumura, T. J. Biol. Chem. (2000) [Pubmed]
  21. ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction. Tagaya, Y., Maeda, Y., Mitsui, A., Kondo, N., Matsui, H., Hamuro, J., Brown, N., Arai, K., Yokota, T., Wakasugi, H. EMBO J. (1989) [Pubmed]
  22. Evidence for a dithiol-activated signaling pathway in natural killer cell avidity regulation of leukocyte function antigen-1: structural requirements and relationship to phorbol ester- and CD16-triggered pathways. Edwards, B.S., Curry, M.S., Southon, E.A., Chong, A.S., Graf, L.H. Blood (1995) [Pubmed]
  23. Mechanism of action of the antifibrogenic compound gliotoxin in rat liver cells. Orr, J.G., Leel, V., Cameron, G.A., Marek, C.J., Haughton, E.L., Elrick, L.J., Trim, J.E., Hawksworth, G.M., Halestrap, A.P., Wright, M.C. Hepatology (2004) [Pubmed]
  24. Singlet oxygen produced by photodynamic action causes inactivation of the mitochondrial permeability transition pore. Salet, C., Moreno, G., Ricchelli, F., Bernardi, P. J. Biol. Chem. (1997) [Pubmed]
  25. DsbB elicits a red-shift of bound ubiquinone during the catalysis of DsbA oxidation. Inaba, K., Takahashi, Y.H., Fujieda, N., Kano, K., Miyoshi, H., Ito, K. J. Biol. Chem. (2004) [Pubmed]
  26. Thioredoxin-catalyzed refolding of disulfide-containing proteins. Pigiet, V.P., Schuster, B.J. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  27. Ebselen: a substrate for human thioredoxin reductase strongly stimulating its hydroperoxide reductase activity and a superfast thioredoxin oxidant. Zhao, R., Masayasu, H., Holmgren, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  28. Generating disulfides enzymatically: reaction products and electron acceptors of the endoplasmic reticulum thiol oxidase Ero1p. Gross, E., Sevier, C.S., Heldman, N., Vitu, E., Bentzur, M., Kaiser, C.A., Thorpe, C., Fass, D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  29. Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. Zhong, L., Arnér, E.S., Holmgren, A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  30. Glutathionylation of trypanosomal thiol redox proteins. Melchers, J., Dirdjaja, N., Ruppert, T., Krauth-Siegel, R.L. J. Biol. Chem. (2007) [Pubmed]
  31. Acute cadmium exposure inactivates thioltransferase (Glutaredoxin), inhibits intracellular reduction of protein-glutathionyl-mixed disulfides, and initiates apoptosis. Chrestensen, C.A., Starke, D.W., Mieyal, J.J. J. Biol. Chem. (2000) [Pubmed]
  32. A novel monothiol glutaredoxin (Grx4) from Escherichia coli can serve as a substrate for thioredoxin reductase. Fernandes, A.P., Fladvad, M., Berndt, C., Andrésen, C., Lillig, C.H., Neubauer, P., Sunnerhagen, M., Holmgren, A., Vlamis-Gardikas, A. J. Biol. Chem. (2005) [Pubmed]
  33. Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms. Lundberg, M., Johansson, C., Chandra, J., Enoksson, M., Jacobsson, G., Ljung, J., Johansson, M., Holmgren, A. J. Biol. Chem. (2001) [Pubmed]
  34. Thioredoxin-2 but not thioredoxin-1 is a substrate of thioredoxin peroxidase-1 from Drosophila melanogaster: isolation and characterization of a second thioredoxin in D. Melanogaster and evidence for distinct biological functions of Trx-1 and Trx-2. Bauer, H., Kanzok, S.M., Schirmer, R.H. J. Biol. Chem. (2002) [Pubmed]
  35. Physiological functions of thioredoxin and thioredoxin reductase. Arnér, E.S., Holmgren, A. Eur. J. Biochem. (2000) [Pubmed]
  36. Mammalian cell-based optimization of the biarsenical-binding tetracysteine motif for improved fluorescence and affinity. Martin, B.R., Giepmans, B.N., Adams, S.R., Tsien, R.Y. Nat. Biotechnol. (2005) [Pubmed]
  37. Iodophenylarsine oxide and arsenical affinity chromatography: new probes for dithiol proteins. Application to tubulins and to components of the insulin receptor-glucose transporter signal transduction pathway. Hoffman, R.D., Lane, M.D. J. Biol. Chem. (1992) [Pubmed]
  38. Gliotoxin causes oxidative damage to plasmid and cellular DNA. Eichner, R.D., Waring, P., Geue, A.M., Braithwaite, A.W., Müllbacher, A. J. Biol. Chem. (1988) [Pubmed]
WikiGenes - Universities