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1. Introduction
2. Chemical world divided to oxidants/antioxidants
3. Oxidants
4. The lesson from Berny Babior
5. The toxic oxidant cocktail
6. Therapeutic approach to treat infectious diseases
7. Selective inhibition of pathogen defense systems
8. Trypanosomatids
9. Hydroperoxide metabolism in mammals
10. Trypanosomes have different oxidants metabolism
11. Unique antioxidants defense in trypanosomes
12. What is trypanothione?
13. The search for TPx homologous to GPx
14. The break through in 1997
15. Oxidoreductases system components
16. Comparing TXN and Trx
17. How does trypanothione interact with TXN?
18. Reduced and oxidized active site of TXN
19. Proof of essentiality of C41 and C43 in TXN
20. The tool to study interaction of TXN - T(SH)2
21. Structure of TXN reacted with a pseudo-substrate
22. First steps of the catalytic cycle
23. Information from site-directed mutagenesis of TXN
24. Tryparedoxin in action
25. Unusual mechanism: the "perverted induced fit"
26. A 2-cysteine peroxiredoxin
27. Pioneering in the field of peroxiredoxins
28. The "new" peroxidase family: peroxiredoxins
29. How does TXNPx interact?
30. General reaction scheme of Prx
31. Variations of the Prx reaction scheme
32. The oxidative steps of the catalytic system
33. Reaction scheme of TXNPx I: oxidative steps
34. N-terminal catalytic triad of a Prx
35. Inter-subunit disulfide formation in TXNPx
36. The reductive steps of the catalytic system
37. Reaction scheme of TXNPx 2: reductive steps
38. TXN attacking TXNPx at the CR (C173')
39. Using same tools to study TXN /TXNPx interaction
40. Tryptic peptides linking TXNPx to TXN C44S
41. Reduced TXNPx from T. cruzi
42. Dead end intermediate of TXNPx and TXNC44S
43. Modeling the intermediate to averaged EM images
44. Shapes of Tb TXNPx
45. MOLISA logo - molecular links of TXN and TXNPx
46. Ranges of rate constants of Prx's
47. Thiol-dependent hydroperoxide metabolism (1)
48. Thiol-dependent hydroperoxide metabolism (2)
49. Other functions of the T(SH)2 TXN couple
50. Nothing works without trypanothione
51. Where should the cycle be arrested?
52. Validation of TryR as drug target
53. Circumstantial evidence for therapeutic validity
54. Inhibition of the biosynthesis of trypanothione
55. Biosynthesis of trypanthione in trypanosomes
56. Validation of TryS as drug target by dsRNAi
57. Simulation of oxidative burst
58. TryS-deficient T.brucei in oxidative challenge
59. HTS for TryS inhibitors
60. MOLISA's new paullone series of TryS inhibitors
61. Summary
62. Acknowledgements
63. Thank you

Topics Covered

• Trypanosomes: causative agents of neglected diseases
• Uniqueness of redox metabolism in trypanosomes
• Detoxification of hydroperoxides and peroxynitrite
• Biosynthesis and function of trypanothione
• Validation of targets for trypanocidal drugs

Links

Series:

• Free Radicals and the Oxygen Paradox

Categories:

• Biochemistry

Talk Citation

Publication History

• Published on November 1, 2007
• Archived on May 31, 2018

Financial Disclosures

• Prof. Leopold Flohe has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.