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

AC1L1AU5     2-amino-4-[[1-[3-[4-[2-[[2- [(4-amino-4...

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 trypanothione


Psychiatry related information on trypanothione

  • In parasites, an additional glutathionylation forms bis-(glutathionyl)-spermidine, trypanothione, believed to be the major surveillance thiol involved in oxidant defense mechanisms in trypanosomatid parasites [6].

High impact information on trypanothione


Chemical compound and disease context of trypanothione


Biological context of trypanothione


Anatomical context of trypanothione


Associations of trypanothione with other chemical compounds


Gene context of trypanothione

  • This structural change may be of functional significance when TryX interacts with tryparedoxin peroxidase, the final protein in the trypanothione-dependent peroxidase pathway [25].
  • The catalytic efficiency of the peroxidase studied here is comparable with that of the peroxiredoxin-like tryparedoxin peroxidases, which shows that trypanosomes possess two distinct peroxidase systems both dependent on the unique dithiol trypanothione [26].
  • The recombinant T. brucei peroxidase has a high preference for the trypanothione/tryparedoxin couple as electron donor for the reduction of different hydroperoxides but accepts also T. brucei thioredoxin [26].
  • When the two amino acid changes Ala34Glu and Arg37Trp are introduced into human GR, the resulting mutant enzyme (GRTR) prefers trypanothione 700-fold over its original substrate, effectively converting a GR into a TR [Bradley, M., Bücheler, U. S., & Walsh, C. T. (1991) Biochemistry 30, 6124-6127] [27].
  • The enzyme trypanothione reductase (TR), together with its substrate, the glutathione-spermidine conjugate trypanothione, plays an essential role in protecting parasitic trypanosomatids against oxidative stress and is a target for drug design [28].

Analytical, diagnostic and therapeutic context of trypanothione


  1. Engineering the substrate specificity of glutathione reductase toward that of trypanothione reduction. Henderson, G.B., Murgolo, N.J., Kuriyan, J., Osapay, K., Kominos, D., Berry, A., Scrutton, N.S., Hinchliffe, N.W., Perham, R.N., Cerami, A. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  2. "Subversive" substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas disease. Henderson, G.B., Ulrich, P., Fairlamb, A.H., Rosenberg, I., Pereira, M., Sela, M., Cerami, A. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  3. Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. Chan, C., Yin, H., Garforth, J., McKie, J.H., Jaouhari, R., Speers, P., Douglas, K.T., Rock, P.J., Yardley, V., Croft, S.L., Fairlamb, A.H. J. Med. Chem. (1998) [Pubmed]
  4. The parasite-specific trypanothione metabolism of trypanosoma and leishmania. Krauth-Siegel, R.L., Meiering, S.K., Schmidt, H. Biol. Chem. (2003) [Pubmed]
  5. Rational drug design using trypanothione reductase as a target for anti-trypanosomal and anti-leishmanial drug leads. Austin, S.E., Khan, M.O., Douglas, K.T. Drug design and discovery. (1999) [Pubmed]
  6. Aldehyde and phosphinate analogs of glutathione and glutathionylspermidine: potent, selective binding inhibitors of the E. coli bifunctional glutathionylspermidine synthetase/amidase. Lin, C.H., Chen, S., Kwon, D.S., Coward, J.K., Walsh, C.T. Chem. Biol. (1997) [Pubmed]
  7. Molecular mechanisms and therapeutic approaches to the treatment of African trypanosomiasis. Wang, C.C. Annu. Rev. Pharmacol. Toxicol. (1995) [Pubmed]
  8. Molecular studies on trypanothione reductase, a target for antiparasitic drugs. Walsh, C., Bradley, M., Nadeau, K. Trends Biochem. Sci. (1991) [Pubmed]
  9. Dual binding sites for translocation catalysis by Escherichia coli glutathionylspermidine synthetase. Pai, C.H., Chiang, B.Y., Ko, T.P., Chou, C.C., Chong, C.M., Yen, F.J., Chen, S., Coward, J.K., Wang, A.H., Lin, C.H. EMBO J. (2006) [Pubmed]
  10. Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. Dumas, C., Ouellette, M., Tovar, J., Cunningham, M.L., Fairlamb, A.H., Tamar, S., Olivier, M., Papadopoulou, B. EMBO J. (1997) [Pubmed]
  11. A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in Leishmania major. Vickers, T.J., Greig, N., Fairlamb, A.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  12. Glutathionylspermidine metabolism in Escherichia coli. Smith, K., Borges, A., Ariyanayagam, M.R., Fairlamb, A.H. Biochem. J. (1995) [Pubmed]
  13. Metabolism and functions of trypanothione in the Kinetoplastida. Fairlamb, A.H., Cerami, A. Annu. Rev. Microbiol. (1992) [Pubmed]
  14. X-ray structure of trypanothione reductase from Crithidia fasciculata at 2.4-A resolution. Kuriyan, J., Kong, X.P., Krishna, T.S., Sweet, R.M., Murgolo, N.J., Field, H., Cerami, A., Henderson, G.B. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  15. Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Mukhopadhyay, R., Dey, S., Xu, N., Gage, D., Lightbody, J., Ouellette, M., Rosen, B.P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  16. Glutathionylspermidine metabolism in Escherichia coli. Purification, cloning, overproduction, and characterization of a bifunctional glutathionylspermidine synthetase/amidase. Bollinger, J.M., Kwon, D.S., Huisman, G.W., Kolter, R., Walsh, C.T. J. Biol. Chem. (1995) [Pubmed]
  17. Trypanosoma brucei and Trypanosoma cruzi tryparedoxin peroxidases catalytically detoxify peroxynitrite via oxidation of fast reacting thiols. Trujillo, M., Budde, H., Piñeyro, M.D., Stehr, M., Robello, C., Flohé, L., Radi, R. J. Biol. Chem. (2004) [Pubmed]
  18. Trypanothione reductase of Trypanosoma congolense: gene isolation, primary sequence determination, and comparison to glutathione reductase. Shames, S.L., Kimmel, B.E., Peoples, O.P., Agabian, N., Walsh, C.T. Biochemistry (1988) [Pubmed]
  19. Sensitivity of parasites to free radical damage by antiparasitic drugs. Docampo, R. Chem. Biol. Interact. (1990) [Pubmed]
  20. S-adenosylmethionine decarboxylase from Leishmania donovani. Molecular, genetic, and biochemical characterization of null mutants and overproducers. Roberts, S.C., Scott, J., Gasteier, J.E., Jiang, Y., Brooks, B., Jardim, A., Carter, N.S., Heby, O., Ullman, B. J. Biol. Chem. (2002) [Pubmed]
  21. Glutathionylation of trypanosomal thiol redox proteins. Melchers, J., Dirdjaja, N., Ruppert, T., Krauth-Siegel, R.L. J. Biol. Chem. (2007) [Pubmed]
  22. Sequence analysis of the tryparedoxin peroxidase gene from Crithidia fasciculata and its functional expression in Escherichia coli. Montemartini, M., Nogoceke, E., Singh, M., Steinert, P., Flohé, L., Kalisz, H.M. J. Biol. Chem. (1998) [Pubmed]
  23. Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. Reckenfelderbäumer, N., Krauth-Siegel, R.L. J. Biol. Chem. (2002) [Pubmed]
  24. Bis(glutathionyl)spermine and other novel trypanothione analogues in Trypanosoma cruzi. Ariyanayagam, M.R., Oza, S.L., Mehlert, A., Fairlamb, A.H. J. Biol. Chem. (2003) [Pubmed]
  25. Tryparedoxins from Crithidia fasciculata and Trypanosoma brucei: photoreduction of the redox disulfide using synchrotron radiation and evidence for a conformational switch implicated in function. Alphey, M.S., Gabrielsen, M., Micossi, E., Leonard, G.A., McSweeney, S.M., Ravelli, R.B., Tetaud, E., Fairlamb, A.H., Bond, C.S., Hunter, W.N. J. Biol. Chem. (2003) [Pubmed]
  26. A second class of peroxidases linked to the trypanothione metabolism. Hillebrand, H., Schmidt, A., Krauth-Siegel, R.L. J. Biol. Chem. (2003) [Pubmed]
  27. Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity. Stoll, V.S., Simpson, S.J., Krauth-Siegel, R.L., Walsh, C.T., Pai, E.F. Biochemistry (1997) [Pubmed]
  28. Kukoamine A and other hydrophobic acylpolyamines: potent and selective inhibitors of Crithidia fasciculata trypanothione reductase. Ponasik, J.A., Strickland, C., Faerman, C., Savvides, S., Karplus, P.A., Ganem, B. Biochem. J. (1995) [Pubmed]
  29. Glyoxalase II of African trypanosomes is trypanothione-dependent. Irsch, T., Krauth-Siegel, R.L. J. Biol. Chem. (2004) [Pubmed]
  30. Redox enzyme engineering: conversion of human glutathione reductase into a trypanothione reductase. Bradley, M., Bücheler, U.S., Walsh, C.T. Biochemistry (1991) [Pubmed]
  31. Overexpression of Crithidia fasciculata trypanothione reductase and crystallization using a novel geometry. Strickland, C.L., Puchalski, R., Savvides, S.N., Karplus, P.A. Acta Crystallogr. D Biol. Crystallogr. (1995) [Pubmed]
  32. Detection by HPLC of a trypanothione synthetase activity in vitro from Entamoeba histolytica. Ondarza, R.N., Hernandez, E., Iturbe, A., Hurtado, G., Tamayo, E.M. Biotechnol. Appl. Biochem. (1999) [Pubmed]
WikiGenes - Universities