R Luise Krauth-Siegel

Summary

Affiliation: University of Heidelberg
Country: Germany

Publications

  1. ncbi request reprint The crystal structure of Plasmodium falciparum glutamate dehydrogenase, a putative target for novel antimalarial drugs
    Christof Werner
    Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, D 35037 Marburg, Germany
    J Mol Biol 349:597-607. 2005
  2. doi request reprint Low-molecular-mass antioxidants in parasites
    R Luise Krauth-Siegel
    Biochemie Zentrum der Universitat Heidelberg, Heidelberg, Germany
    Antioxid Redox Signal 17:583-607. 2012
  3. ncbi request reprint Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism
    R Luise Krauth-Siegel
    Biochemie Zentrum der Universitat Heidelberg, 69120 Heidelberg, Germany
    Biochim Biophys Acta 1780:1236-48. 2008
  4. pmc Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei
    Tanja Schlecker
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    Biochem J 405:445-54. 2007
  5. ncbi request reprint Glutathionylation of trypanosomal thiol redox proteins
    Johannes Melchers
    Biochemie Zentrum, Universitat, Heidelberg, Germany
    J Biol Chem 282:8678-94. 2007
  6. ncbi request reprint Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1
    Michael Filser
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, D 69120 Heidelberg, Germany
    Biol Chem 389:21-32. 2008
  7. ncbi request reprint Glyoxalase II of African trypanosomes is trypanothione-dependent
    Thorsten Irsch
    Biochemie Zentrum der Universitat Heidelberg, 69120 Heidelberg, Germany
    J Biol Chem 279:22209-17. 2004
  8. pmc Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes
    Marcelo A Comini
    Centre of Biochemistry, Heidelberg University, Im Neuenheimer Feld 504, D 69120, Heidelberg, Germany
    Biochem J 402:43-9. 2007
  9. doi request reprint Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products
    Kathrin Buchholz
    Biochemie Zentrum der Universitat Heidelberg, INF 504, D 69120 Heidelberg, Germany
    Mol Biochem Parasitol 160:65-9. 2008
  10. doi request reprint A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage
    Michael Diechtierow
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
    Free Radic Biol Med 51:856-68. 2011

Collaborators

Detail Information

Publications42

  1. ncbi request reprint The crystal structure of Plasmodium falciparum glutamate dehydrogenase, a putative target for novel antimalarial drugs
    Christof Werner
    Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, D 35037 Marburg, Germany
    J Mol Biol 349:597-607. 2005
    ..These findings might be exploited for the design of peptidomimetics capable of disrupting the oligomeric organisation of the parasite enzyme...
  2. doi request reprint Low-molecular-mass antioxidants in parasites
    R Luise Krauth-Siegel
    Biochemie Zentrum der Universitat Heidelberg, Heidelberg, Germany
    Antioxid Redox Signal 17:583-607. 2012
    ..Parasitic organisms show a remarkable diversity with respect to the nature and functions of their main low-molecular-mass antioxidants and many of them developed pathways that do not have a counterpart in their mammalian hosts...
  3. ncbi request reprint Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism
    R Luise Krauth-Siegel
    Biochemie Zentrum der Universitat Heidelberg, 69120 Heidelberg, Germany
    Biochim Biophys Acta 1780:1236-48. 2008
    ..Thus, cellular thiol redox homeostasis is maintained by the biosynthesis and reduction of trypanothione. Nearly all proteins of the parasite-specific trypanothione metabolism have proved to be essential...
  4. pmc Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei
    Tanja Schlecker
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    Biochem J 405:445-54. 2007
    ..The catalytic mechanism of the Tpx peroxidase resembles that of atypical 2-Cys-peroxiredoxins but is distinct from that of the selenoenzymes...
  5. ncbi request reprint Glutathionylation of trypanosomal thiol redox proteins
    Johannes Melchers
    Biochemie Zentrum, Universitat, Heidelberg, Germany
    J Biol Chem 282:8678-94. 2007
    ..Also glyoxalase II and Trypanosoma cruzi trypanothione reductase were not sensitive to thiolation at physiological GSSG concentrations...
  6. ncbi request reprint Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1
    Michael Filser
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, D 69120 Heidelberg, Germany
    Biol Chem 389:21-32. 2008
    ..This is surprising because even bacterial and plant 1-Cys-glutaredoxins efficiently revert the defects, and may be due to the lack of two basic residues conserved in all but the trypanosomatid proteins...
  7. ncbi request reprint Glyoxalase II of African trypanosomes is trypanothione-dependent
    Thorsten Irsch
    Biochemie Zentrum der Universitat Heidelberg, 69120 Heidelberg, Germany
    J Biol Chem 279:22209-17. 2004
    ..Our results show that the glyoxalase system is another pathway in which the nearly ubiquitous glutathione is replaced by the unique trypanothione in trypanosomatids...
  8. pmc Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes
    Marcelo A Comini
    Centre of Biochemistry, Heidelberg University, Im Neuenheimer Feld 504, D 69120, Heidelberg, Germany
    Biochem J 402:43-9. 2007
    ..5-fold, the sensitivity against exogenously generated H2O2 was significantly enhanced. The results prove the essential role of the cTXN and its pivotal function in the parasite defence against oxidative stress...
  9. doi request reprint Cytotoxic interactions of methylene blue with trypanosomatid-specific disulfide reductases and their dithiol products
    Kathrin Buchholz
    Biochemie Zentrum der Universitat Heidelberg, INF 504, D 69120 Heidelberg, Germany
    Mol Biochem Parasitol 160:65-9. 2008
    ..Since MB is an affordable, available, and accessible drug it might be tested--alone or in drug combinations--against trypanosomatid-caused diseases of animal and man...
  10. doi request reprint A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage
    Michael Diechtierow
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
    Free Radic Biol Med 51:856-68. 2011
    ..Cells lacking specifically the mitochondrial Px III showed a transient growth retardation and cardiolipin peroxidation but adapted within 24h to normal proliferation...
  11. ncbi request reprint Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei
    Tanja Schlecker
    Biochemie Zentrum der Universitat Heidelberg, Germany
    J Biol Chem 280:14385-94. 2005
    ..Thus, the cellular functions of the glutathione peroxidase-type enzymes cannot be taken over by the 2 Cys-peroxiredoxins that also occur in the cytosol and mitochondrion of the parasite...
  12. ncbi request reprint Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei
    Heide Schmidt
    Biochemie Zentrum Heidelberg, Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    J Biol Chem 278:46329-36. 2003
    ..Obviously, a specific thioredoxin reductase is not required as thioredoxin reduction can be conducted by the parasite-specific trypanothione/trypanothione reductase system...
  13. pmc Dissecting the catalytic mechanism of Trypanosoma brucei trypanothione synthetase by kinetic analysis and computational modeling
    Alejandro E Leroux
    Biochemie Zentrum der Universitat Heidelberg, D 69120 Heidelberg, Germany
    J Biol Chem 288:23751-64. 2013
    ..The newly detected concerted substrate and product inhibition suggests that TryS activity is tightly regulated. ..
  14. ncbi request reprint Enzymes of the trypanothione metabolism as targets for antitrypanosomal drug development
    Armin Schmidt
    Biochemie Zentrum Heidelberg, Ruprecht Karls Universitat, Im Neuenheimer Feld 328, Heidelberg, 69120, Germany
    Curr Top Med Chem 2:1239-59. 2002
    ..The most effective inhibitors of the enzymes known to date, their mode of action, and the (dis)advantages of different types of inhibitors as potential drug candidates will be discussed...
  15. doi request reprint Glyoxalase II does not support methylglyoxal detoxification but serves as a general trypanothione thioesterase in African trypanosomes
    Alexandra Wendler
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    Mol Biochem Parasitol 163:19-27. 2009
    ..brucei glyoxalase II. This offers a function for the parasite glyoxalase II as general trypanothione thioesterase independent of ketoaldehyde detoxification...
  16. ncbi request reprint Preparative enzymatic synthesis of trypanothione and trypanothione analogues
    Marcelo A Comini
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    Int J Parasitol 39:1059-62. 2009
    ..The protocol also allows the synthesis of related glutathione conjugates. It will greatly facilitate the thorough analysis of this parasite's metabolism and drug screening approaches against trypanothione-dependent enzymes...
  17. pmc The dithiol glutaredoxins of african trypanosomes have distinct roles and are closely linked to the unique trypanothione metabolism
    Sevgi Ceylan
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    J Biol Chem 285:35224-37. 2010
    ..Grx1 and, less efficiently, also Grx2 catalyze the reduction of GSSG by trypanothione. Thus, the Grxs play exclusive roles in the trypanothione-based thiol redox metabolism of African trypanosomes...
  18. ncbi request reprint A second class of peroxidases linked to the trypanothione metabolism
    Henning Hillebrand
    Biochemie Zentrum Heidelberg, Universitat Heidelberg, 69120 Heidelberg, Germany
    J Biol Chem 278:6809-15. 2003
    ....
  19. doi request reprint Unsaturated Mannich bases active against multidrug-resistant Trypanosoma brucei brucei strains
    I Nicole Wenzel
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    ChemMedChem 4:339-51. 2009
    ..brucei brucei suggesting alternative drug uptake routes. The Michael acceptor properties of the three most active compounds towards glutathione correlated with the observed trypanocidal activities...
  20. ncbi request reprint Trypanothione and tryparedoxin in ribonucleotide reduction
    R Luise Krauth-Siegel
    Biochemie Zentrum Heidelberg, Universitat Heidelberg, 69120 Heidelberg, Germany
    Methods Enzymol 347:259-66. 2002
  21. ncbi request reprint Parasite-specific trypanothione reductase as a drug target molecule
    R Luise Krauth-Siegel
    Biochemie Zentrum Heidelberg, Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    Parasitol Res 90:S77-85. 2003
    ..The (dis)advantages of the different types of compounds as potential drug candidates as well as modern computer-based approaches to the identification of new leads are discussed...
  22. doi request reprint Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei
    Angela Roldán
    Biochemie Zentrum der Universität Heidelberg BZH, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
    Mol Microbiol 81:623-39. 2011
    ..Since the medium used for the cultivation of procyclic cells was not supplemented with glucose, impairment of the 2-ketoglutarate dehydrogenase complex is probably the main effect of LipDH depletion...
  23. ncbi request reprint Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia
    R Luise Krauth-Siegel
    Universitat Heidelberg, Biochemie Zentrum, Im Neuenheimer Feld 504, D 69120 Heidelberg, Germany
    Angew Chem Int Ed Engl 44:690-715. 2005
    ..Inhibitors of antioxidant enzymes such as trypanothione reductase are, indeed, parasiticidal but they can also delay or prevent resistance against a number of other antiparasitic drugs...
  24. pmc High throughput screening against the peroxidase cascade of African trypanosomes identifies antiparasitic compounds that inactivate tryparedoxin
    Florian Fueller
    Biochemie Zentrum der Universitat Heidelberg, Heidelberg, Germany
    J Biol Chem 287:8792-802. 2012
    ....
  25. ncbi request reprint Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate
    Brittany Lee
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany
    J Med Chem 48:7400-10. 2005
    ..Interaction of these compounds with both trypanothione and trypanothione reductase could account for their potent trypanocidal effect against Trypanosoma brucei...
  26. doi request reprint Biological activities of xanthatin from Xanthium strumarium leaves
    Endalkachew Nibret
    Institut für Pharmazie und molekulare Biotechnologie, Universitat Heidelberg, Im Neuenheimer Feld 364, 69120, Heidelberg, Germany
    Phytother Res 25:1883-90. 2011
    ....
  27. ncbi request reprint Cytosolic peroxidases protect the lysosome of bloodstream African trypanosomes from iron-mediated membrane damage
    Corinna Hiller
    Biochemie Zentrum der Universität Heidelberg BZH, Heidelberg, Germany
    PLoS Pathog 10:e1004075. 2014
    ..brucei. The respective knockout of the cytosolic px I-II in the procyclic insect form resulted in cells that were fully viable in Trolox-free medium. ..
  28. doi request reprint Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum
    Tolga Eichhorn
    Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
    Biochem Pharmacol 85:38-45. 2013
    ..The regions covered by these residues are known to be functionally important for TCTP function. We conclude that interaction of artemisinin with TCTP may be at least in part explain the antimalarial activity of artemisinin...
  29. ncbi request reprint Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin
    Nina Reckenfelderbäumer
    Biochemie Zentrum Heidelberg, Universitat Heidelberg, 69120 Heidelberg, Germany
    J Biol Chem 277:17548-55. 2002
    ..0. The fact that the pK value of tryparedoxin coincides with the intracellular pH of the parasite may contribute to the reactivity of tryparedoxin in thiol disulfide exchange reactions...
  30. ncbi request reprint The parasite-specific trypanothione metabolism of trypanosoma and leishmania
    R Luise Krauth-Siegel
    Center of Biochemistry, University of Heidelberg, Im Neuenheimer Feld 504, D 69120 Heidelberg, Germany
    Biol Chem 384:539-49. 2003
    ....
  31. ncbi request reprint Overexpression of the putative thiol conjugate transporter TbMRPA causes melarsoprol resistance in Trypanosoma brucei
    Sanjay K Shahi
    ZMBH, Im Neuenheimer Feld 282, D 69120 Heidelberg, Germany
    Mol Microbiol 43:1129-38. 2002
    ..Overexpression of TbMRPE had little effect on susceptibility to melarsoprol but did give two- to threefold resistance to suramin...
  32. ncbi request reprint Coupling of a competitive and an irreversible ligand generates mixed type inhibitors of Trypanosoma cruzi trypanothione reductase
    Oliver Inhoff
    Biochemie Zentrum, Heidelberg University, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    J Med Chem 45:4524-30. 2002
    ....
  33. ncbi request reprint Phenothiazine radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase: enzyme protection by radical scavengers
    José Gutiérrez-Correa
    Bioenergetics Research Centre, School of Medicine, University of Buenos Aires, Paraguay 2155, 1121 Bueno Aires, Argentina
    Free Radic Res 37:281-91. 2003
    ..The role of the observed effects of PTZ radicals for PTZ cytotoxicity is discussed...
  34. ncbi request reprint Betraying the parasite's redox system: diaryl sulfide-based inhibitors of trypanothione reductase: subversive substrates and antitrypanosomal properties
    Bernhard Stump
    Laboratorium fur Organische Chemie, ETH Zurich, Honggerberg, HCI, 8093 Zurich, Switzerland
    ChemMedChem 2:1708-12. 2007
  35. ncbi request reprint Thiol-based redox metabolism of protozoan parasites
    Sylke Muller
    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, DD1 5EH, Dundee, UK
    Trends Parasitol 19:320-8. 2003
    ..In Plasmodium falciparum, the crystal structures of glutathione reductase and glutamate dehydrogenase are now available; another drug target, thioredoxin reductase, has been demonstrated to be essential for the malarial parasite...
  36. ncbi request reprint Structure of thioredoxin from Trypanosoma brucei brucei
    Rosmarie Friemann
    Department of Molecular Biosciences, Swedish University of Agricultural Sciences, Biomedical Center, Box 590, S 75124 Uppsala, Sweden
    FEBS Lett 554:301-5. 2003
    ..The conserved Trp in the WCGPC sequence motif has an exposed position that can interact with target proteins...
  37. doi request reprint Monothiol glutaredoxin-1 is an essential iron-sulfur protein in the mitochondrion of African trypanosomes
    Marcelo A Comini
    Centre of Biochemistry, Heidelberg University, Im Neuenheimer Feld 504, D 69120 Heidelberg, Germany
    J Biol Chem 283:27785-98. 2008
    ..The results point to an essential role of the mitochondrial 1-C-Grx1 in the iron metabolism of these parasites...
  38. ncbi request reprint Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets
    Lucia Otero
    Departamento Estrella Campos, Facultad de Quimica, Universidad de la Republica, Montevideo, Uruguay
    J Med Chem 49:3322-31. 2006
    ..Moreover, the complexes were found to be irreversible inhibitors of trypanothione reductase...
  39. ncbi request reprint In vivo anti-Chagas vinylthio-, vinylsulfinyl-, and vinylsulfonylbenzofuroxan derivatives
    Williams Porcal
    Departamento de Quimica Organica, Facultad de Ciencias and Facultad de Química, Universidad de la Republica, Montevideo, Uruguay
    J Med Chem 50:6004-15. 2007
    ..Furthermore, the compounds showed good in vivo activities when they were studied in an acute murine model of Chagas' disease. The compounds were able to reduce the parasite loads of animals with fully established T. cruzi infections...
  40. ncbi request reprint Silencing of the thioredoxin gene in Trypanosoma brucei brucei
    Armin Schmidt
    Biochemie Zentrum Heidelberg, Ruprecht Karls Universitat, Im Neuenheimer Feld 504, D 69120 Heidelberg, Germany
    Mol Biochem Parasitol 125:207-10. 2002
  41. ncbi request reprint Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis
    Svea Meiering
    Biochemie Zentrum, Universitat Heidelberg, Im Neuenheimer Feld 504, D 69120 Heidelberg, Germany
    J Med Chem 48:4793-802. 2005
    ..Remarkably, all three derivatives carried two copies of an identical 2-methoxy-4-methyl-1-(phenylmethoxy)benzene substituent...
  42. ncbi request reprint Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator deferoxamine
    Tanja Breidbach
    Abteilung Parasitologie, Hygiene Institut der Ruprecht Karls Universität, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
    Int J Parasitol 32:473-9. 2002
    ..The results have implications for antitrypanosomal drug development based on specific intervention with the parasite's iron metabolism...