Enzymes of parasite thiol metabolism as drug targets

Parasitology Today

Volumn 15, Issue 10, 1999, Pages 404-409

  Krauth Siegel, R Luise ^a   Coombs, Graham H ^b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; ENZYME; OXIDOREDUCTASE; THIOL; THIOREDOXIN; TRYPANOTHIONE;

CHEMOTHERAPY; DRUG TARGETING; ENZYME ANALYSIS; ENZYME INHIBITION; MEDICAL RESEARCH; METABOLISM; NONHUMAN; PARASITE; REVIEW; SYNTHESIS;

ANIMALS; ANTIPROTOZOAL AGENTS; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; GLUTATHIONE; LEISHMANIA; NADH, NADPH OXIDOREDUCTASES; PLASMODIUM; PROSPECTIVE STUDIES; SPERMIDINE; SULFHYDRYL COMPOUNDS; THIOREDOXIN REDUCTASE (NADPH);

EID: 0033215010     PISSN: 01694758     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0169-4758(99)01516-1     Document Type: Review

References (48)

1. Fairlamb A.H., Cerami A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu. Rev. Microbiol. 46:1992;695-729.
2. Krauth-Siegel R.L., Lüdemann H. Reduction of dehydroascorbate by trypanothione. Mol. Biochem. Parasitol. 80:1996;203-208.
3. Tetaud E.et al. Cloning and characterization of the two enzymes responsible for trypanothione synthesis in Crithidia fasciculata. J. Biol. Chem. 273:1998;19383-19390.
4. Nogoceke E.et al. A unique cascade of oxidoreductases catalyses trypanothione-mediated peroxide metabolism in Crithidia fasciculata. Biol. Chem. 378:1997;827-836.
5. Gommel D.U.et al. Catalytic characteristics of tryparedoxin. Eur. J. Biochem. 248:1997;913-918.
6. Montemartini M.et al. Sequence, heterologous expression and functional characterization of a novel tryparedoxin from Crithidia fasciculata. Biol. Chem. 379:1998;1137-1142.
7. Tetaud E., Fairlamb A.H. Cloning, expression and reconstitution of the trypanothione-dependent peroxidase system of Crithidia fasciculata. Mol. Biochem. Parasitol. 96:1998;111-123.
8. Levick M.P.et al. Identification and characterisation of a functional peroxidoxin from Leishmania major. Mol. Biochem. Parasitol. 96:1998;125-137.
9. Lüdemann H.et al. Trypanosoma brucei tryparedoxin, a thioredoxin-like protein in African trypanosomes. FEBS Lett. 431:1998;381-385.
10. Mukhopadhyay R.et al. Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Proc. Natl. Acad. Sci. U. S. A. 93:1996;10383-10387.
11. Légaré D.et al. Efflux systems and increased trypanothione levels in arsenite-resistant Leishmania. Exp. Parasitol. 87:1997;275-282.
12. Grondin K.et al. Co-amplification of the γ-glutamylcysteine synthetase gene gsh1 and of the ABC transporter gene pgpA in arsenite-resistant Leishmania tarentolae. EMBO J. 16:1997;3057-3065.
13. Dumas C.et al. Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J. 16:1997;2590-2598.
14. Tovar J.et al. Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus. Mol. Microbiol. 29:1998;653-660.
15. Tovar J.et al. Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a trans-dominant mutant homologue: effect on parasite intracellular survival. Proc. Natl. Acad. Sci. U. S. A. 95:1998;5311-5316.
16. Wirtz E., Clayton C. Inducible gene expression in trypanosomes mediated by a prokaryotic repressor. Science. 268:1995;1179-1183.
17. O'Sullivan M.C.et al. Polyamine derivatives as inhibitors of trypanothione reductase and assessment of their trypanocidal activities. Bioorg. Med. Chem. 5:1997;2145-2155.
18. Moreno S.N.J.et al. Inhibition of Trypanosoma cruzi trypanothione reductase by crystal violet. Mol. Biochem. Parasitol. 67:1994;313-320.
19. Jacoby E.M.et al. Crystal structure of the Trypanosoma cruzi trypanothione reductase-mepacrine complex. Protein Struct. Funct. Genet. 24:1996;73-80.
20. Faerman C.H.et al. Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors. Bioorg. Med. Chem. 4:1996;1247-1253.
21. Chan C.et al. Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs. J. Med. Chem. 41:1998;148-156.
22. Benson T.J.et al. Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. Biochem. J. 286:1992;9-11.
23. Krauth-Siegel R.L.et al. Stevenson K.J., Massey V., Williams C.H. Jr. Flavins and Flavoproteins. 1996;35-44 University of Calgary Press.
24. Fernandez-Gomez R.et al. 2-Amino diphenylsulfides as new inhibitors of trypanothione reductase. Int. J. Antimicrob. Agents. 6:1995;111-118.
25. Bailey S.et al. Substrate interactions between trypanothione reductase and N1-glutathionylspermidine disulphide at 0.28-nm resolution. Eur. J. Biochem. 213:1993;67-75.
26. Bond C.S.et al. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure. 7:1999;81-89.
27. Morrison, J. and Walsh, C.T. (1988) in Advances in Enzymology and Related Areas of Molecular Biology (Vol. 61) (Meister, A., ed.), pp 201-301, John Wiley & Sons.
28. Schirmer R.H., Müller J., Krauth-Siegel R.L. Disulfide-reductase inhibitors as chemotherapeutic agents: the design of drugs for trypanosomiasis and malaria. Angew. Chem., Int. Ed. Engl. 34:1995;141-154.
29. Schöneck R.et al. Cloning, sequencing and functional expression of dihydrolipoamide dehydrogenase from the human pathogen Trypanosoma cruzi. Eur. J. Biochem. 243:1997;739-747.
30. Sreider C.M.et al. Superoxide anion production by lipoamide dehydrogenase redox-cycling: effect of enzyme modifiers. Biochem. Int. 23:1991;83-92.
31. Blumenstiel K.et al. Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase. Biochem. Pharmacol. 1999;. (in press).
32. Gallwitz H.et al. Ajoene is an inhibitor and subversive substrate of human glutathione reductase and T. cruzi trypanothione reductase. Crystallographic, kinetic, and spectroscopic studies. J. Med. Chem. 42:1999;364-372.
33. Verbruggen C.et al. Phosphonic acid and phosphinic acid tripeptides as inhibitors of glutathionylspermidine synthetase. Bioorg. Med. Chem. Lett. 6:1996;253-258.
34. Chen S.et al. Novel inhibitors of trypanothione biosynthesis: synthesis and evaluation of a phosphinate analog of glutathionyl spermidine (Gsp), a potent, slow-binding inhibitor of Gsp synthetase. Bioorg. Med. Chem. Lett. 7:1997;505-510.
35. Atamna H., Ginsburg H. The malaria parasite supplies glutathione to its host cell. Investigation of glutathione transport and metabolism in human erythrocytes infected with Plasmodium falciparum. Eur. J. Biochem. 250:1997;670-679.
36. Ayi K.et al. Plasmodium falciparum glutathione metabolism and growth are independent of glutathione system of host erythrocytes. FEBS Lett. 424:1998;257-261.
37. Zhang Y.et al. Glutathione reductase-deficient erythrocytes as host cells of malarial parasites. Biochem. Pharmacol. 37:1988;861-865.
38. Färber P.M.et al. Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 422:1998;311-314.
39. Dubois V.L.et al. Plasmodium bergei: implication of intracellular glutathione and its related enzyme in chloroquine resistance in vivo. Exp. Parasitol. 81:1995;117-124.
40. Luersen K., Walter R.D., Müller S. The putative γ-glutamylcysteine synthetase from Plasmodium falciparum contains large insertions and a variable tandem repeat. Mol. Biochem. Parasitol. 98:1998;131-142.
41. Arscott L.D.et al. The mechanism of thioredoxin reductase from human placenta is similar to the mechanisms of lipoamide dehydrogenase and glutathione reductase and is distinct from the mechanism of thioredoxin reductase from Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 94:1997;3621-3626.
42. Gromer S.et al. Human placenta thioredoxin reductase. Isolation of the selenoenzyme, steady state kinetics, and inhibition by therapeutic gold compounds. J. Biol. Chem. 273:1998;20096-20101.
43. Gilberger T.W., Walter R.D., Müller S. Identification and characterization of the functional amino acids at the active site of the large thioredoxin reductase from Plasmodium falciparum. J. Biol. Chem. 272:1997;29584-29589.
44. Gilberger T.W.et al. The role of the C-terminus for catalysis of the large thioredoxin reductase from Plasmodium falciparum. FEBS Lett. 425:1998;407-410.
45. Wang P-F.et al. Thioredoxin reductase from Plasmodium falciparum: evidence for the interaction between the C-terminal cysteine residues and the active site disulfide-dithiol. Biochemistry. 38:1999;3187-3196.
46. Müller S.et al. Recombinant putative glutathione reductase from Plasmodium falciparum exhibits thioredoxin reductase activity. Mol. Biochem. Parasitol. 80:1996;215-219.
47. Dandekar T.et al. Conservation of gene order: a fingerprint of physically interacting proteins. Trends Biochem. Sci. 23:1998;324-328.
48. Barrett M.P., Mottram J.C., Coombs G.H. Recent advances in identifying and validating drug targets in trypanosomes and leishmanias. Trends Microbiol. 7:1999;82-88.