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2000 | 47 | 1 | 173-180
Article title

ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral therapy.

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EN
Abstracts
EN
To enhance the inhibitory potential of 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) vs hepatitis C virus (HCV) NTPase/helicase, ribavirin-5'-triphosphate (ribavirin-TP) was synthesized and investigated. Ribavirin-TP was prepared with the use of modified Yoshikawa-Ludwig-Mishra-Broom procedure (cf. Mishra & Broom, 1991, J. Chem. Soc., Chem. Commun, 1276-1277) involving phosphorylation of unprotected nucleoside. Kinetic analysis revealed enhanced inhibitory potential of ribavirin-TP (IC50=40 μM) as compared to ribavirin (IC50 > 500 μM). Analysis of the inhibition type by means of graphical methods showed a competitive type of inhibition with respect to ATP. In view of the relatively low specificity towards nucleoside-5'-triphosphates (NTP) of the viral NTPase/helicases, it could not be ruled out that the investigated enzyme hydrolyzed the ribavirin-TP to less potent products. Investigations on non- hydrolysable analogs of ribavirin-TP or ribavirin-5'-diphosphate (ribavirin-DP) are currently under way.
Year
Volume
47
Issue
1
Pages
173-180
Physical description
Dates
published
2000
received
1999-10-25
References
  • 1. Choo, Q.-L., Kuo, G., Weiner, A.J., Overby, L. R., Bradley, D. W. & Houghton, M. (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244, 359-362.
  • 2. Choo, Q.-L., Weiner, A J., Overby, L.R, Kuo, G. & Houghton, M. (1990) Hepatitis C virus: The major causative agent of viral non-A, non-B hepatitis. Br. Med. Bull. 46, 423-441.
  • 3. Takamizawa, A., Mori, C., Fuke, I., Manabe, S., Murakami, S., Fujita, J., Onoshi, E., Andoh, T., Yoshida, I. & Okayama, H. ( 1991) Structure and organization of the hepatitis C virus genome isolated from human carriers. J. Virol. 65, 1105-1113.
  • 4. Van Doorn, L.-J. (1994) Review: Molecular biology of the hepatitis C virus. J. Med. Virol. 43, 345-356.
  • 5. Miller, R.H. & Purcell, R.H. (1990) Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proc. Natl. Acad. Sci. U.S.A. 87, 2057-2061.
  • 6. Suzich, J., Tamura, J., Palmer-Hill, F., Warrener, P., Grakoui, A., Rice, C., Feinstone, S. & Collett, M. (1993) Hepatitis C virus NS3 protein polynucleotide-stimulated nucleoside triphosphatase and comparison with the related pestivirus and flavivirus enzymes. J. Virol. 67, 6152-6158.
  • 7. Tai, C-L., Chi, W.-K., Chen, D.-S. & Hwang, L.-H. (1996) The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3). J. Virol. 70, 8477-8484.
  • 8. Kadare, G. & Haenni, A.L, (1997) Virus-encoded RNA helicase. J. Virol. 71, 2583- 2590.
  • 9. Gorbalenya, A.E. & Koonin, E.V. (1993) Helicases: Amino acid sequence comparisons and structure-function relationships. Curr. Opin. Struct. Biol. 3, 419-429.
  • 10. Yao, N., Hesson, T., Cable, M., Hong, Z., Kwong, A.D., Le, H.V. & Weber, P.C. (1997) Structure of the hepatitis C virus RNA helicase domain. Nature Struct. Biol. 4, 463-467.
  • 11. Kim, J., Morgenstern, K., Griffith, J., Dwyer, M., Thomson, J., Murcko, M., Lin, C. & Caron, P. (1998) Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: The crystal structure provides insights into the mode of unwinding. Structure 6, 89-100.
  • 12. Borowski, P., Kuehl, R., Mueller, O., Hwang, L.-H., Schulze zur Wiesch, J. & Schmitz, B. (l999) Biochemical properties of a minimal functional domain with ATP-binding activity of the NTPase/helicase of hepatitis C virus. Eur. J. Biochem. 266, 715-723.
  • 13. Walker, J.E., Saraste, M., Runswick, M.J. & Gay, N.J. (1982) Distantly related sequences in the α- and β-subunits of ATP synthase, myosin, kinases and other ATP- requiring enzymes and a common nucleotide binding fold. EMBO J. 1, 945-951.
  • 14. Black, M.E. & Hruby, D.E. (1992) Site-directed mutagenesis of a conserved domain in vaccinia virus thymidine kinase. Evidence for a potential role in magnesium binding. J. Biol. Chem. 267, 6801-6806.
  • 15. Yan, H.G. & Tsai, M.D. (1991) Mechanism of adenylate kinase. Demonstration of a functional relationship between aspartate 93 and Mg 2+ by site-directed mutagenesis and proton, phosphorus-31, and magnesium-25 NMR. Biochemistry 30, 5539-5546.
  • 16. Shuman, S. (1992) Vaccinia virus RNA helicase: An essential enzyme related to the DE-H family of RNA-dependent NTPases. Proc. Natl. Acad. Sci. U.S.A. 89, 10935- 10939.
  • 17. Wagner, J.D.O., Jankowsky, E., Company, M. Pyle, A.M. & Abelson, J.N. (1998) The DEAH- box protein PRP22 is an ATPase that mediates ATP-dependent mRNA release from the spliceosome and unwinds RNA duplexes. EMBO J. 17, 2926-2937.
  • 18. Kyono, K., Miyashiro, M. & Taguchi, I. (1998) Detection of hepatitis C virus helicase activity using scintillation proximity assay system. Anal. Biochem. 257, 120-126.
  • 19. Chen, P.S., Jr, Toribara, T.Y. & Warner, H. (1956) Microdetermination of phosphorus. Anal. Chem. 28, 1756-1758.
  • 20. Yoshikawa, M., Kato, T. & Takenishi, T. (1967) A novel method of phosphorylation of nucleosides to 5'-nucleotides. Tetrahedron Lett. 50, 5065-5068.
  • 21. Ludwig, J. (1981) Chemical synthesis of nucleoside triphosphates. Acta Biochim. et Biophys. Acad. Sci. Hung. 16, 131-133.
  • 22. Mishra, N.C. & Broom, A.D. (1991) A novel synthesis of nucleoside 5'-triphosphates. J. Chem. Soc., Chem. Commun. 1276-1277.
  • 23. Borowski, P., Medem, S. & Laufs, R. (1993) Biochemical properties of a novel 28 kDa protein tyrosine kinase partially purified from the particulate fraction of rat spleen. Biochem. Biophys. Res. Commun. 197, 646-653.
  • 24. Borowski, P., Kornetzky, L. & Laufs, R. (l998) Properties of the proteolytically generated catalytic domain (42 kDa kinase) of epidermal growth factor receptor: Comparison with holoenzyme. J. Biochem. 123, 380-385.
  • 25. Preugschat, F., Averett, D.R., Clarke, B.E. & Porter, D.J. (1996) A steady-state and pre- steady-state kinetic analysis of the NTPase activity associated with the hepatitis C virus NS3 helicase domain. J. Biol. Chem. 271, 24449-24459.
  • 26. Smith, R.A. (1980). Mechanism of action of ribavirin; in Ribavirin a Broad Spectrum Antiviral Agent (Smith, R.A. & Kirkapatrick, W., eds.) pp. 99-118, Academic Press, New York.
  • 27. Porter, D. (1998) A kinetic analysis of the oligonucleotide-modulated ATPase activity of the helicase domain of the NS3 protein from hepatitis C virus 3. J. Biol. Chem. 273, 14247- 14253.
  • 28. Miller, J.P., Kigwana, L.J., Streeter, D.G., Robins, R.K., Simon, L.N. & Roboz, J. (1977) The relationship between the metabolism of ribavirin and its proposed mechanism of action. Ann. N.Y. Acad. Sci. U.S.A. 284, 211- 229.
  • 29. Zimmerman, T.P. & Deeprose, R.D. (1978) Metabolism of 5-amino-1-β-D-ribafuranosylimidazole-4-carboxamide and related five-membered heterocycles to 5'-triphoshates in human blood and L5178Y cells. Biochem. Pharmacol. 27, 709-716.
  • 30. Dixon, M. (1952) The determination of enzyme inhibitor constants. Biochem. J. 55, 170-171.
  • 31. Cornish-Bowden, A. (1974) A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non-competitive inhibitors. Biochem. J. 137 143-144.
  • 32. Warrener, P. & Collett, M. (1995) Pestivirus NS3 (p80) protein possesses RNA helicase activity. J. Virol. 69, 1720-1726.
  • 33. Tamura, J., Warrener, P. & Collett, M. (1993) RNA-stimulated NTPase activity associated with the p80 protein of the pestivirus bovine viral diarrhea virus. Virology 193, 1-l0.
  • 34. Lain, S., Martin, M., Riechmann, J.L. & Garcia, J.A. (1991) Novel catalytic activity associated with positive strand RNA virus infection: Nucleic acid stimulated ATPase activity of the plum pox potyvirus helicaselike protein. J. Virol. 65, 1-6.
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Publication order reference
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bwmeta1.element.bwnjournal-article-abpv47i1p173kz
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