Structure and Function of Hepatitis C Virus NS3 Helicase

  • A. D. Kwong
  • J. L. Kim
  • C. Lin
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 242)

Abstract

Hepatitis C virus (HCV) is a positive-stranded RNA virus with a linear RNA genome approximately 9.6kb in size (CHOO et al. 1989). This genome encodes a single polyprotein of approximately 3010 amino acids and at least ten viral proteins: NH2-C-E1 -E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-COOH (CHOO et al. 1991; KAITO et al. 1994; RICE 1996; TAKAMIZAWA et al. 1991). The individual proteins are released from the polyprotein by both host signal peptidases and viral proteases (GRAKOUI et al. 1993; HIJIKATA et al. 1991; LIN et al. 1994 and reviewed by Reed and Rice elsewhere in this volume (pp 55–84)). Some or all of the nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and NS5B) are believed to interact to form the viral replication machinery (HOUGHTON 1996; RICE 1996).

Keywords

Recombination Adenosine Bacillus Arginine Alanine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bartenschlager R (1997) Candidate targets for hepatitis C virus-specific antiviral therapy. Intervirology 40:378–393PubMedCrossRefGoogle Scholar
  2. Bartenschlager R, Lohmann V, Wilkinson T, Koch JO (1995) Complex formation between the NS3 Serine-type proteinase of the hepatitis C virus and NS4A and its importance for polyprotein maturation. J Virol 69:7519–7528PubMedGoogle Scholar
  3. Bayliss CD, Smith GL (1996) Vaccinia virion protein 18R has both DNA and RNA helicase activities implications for vaccinia virus transcription. J Virol 70:794–800PubMedGoogle Scholar
  4. Bilderback T, Fulmer T, Mantulin WW, Glaser M (1996) Substrate binding causes movement in the ATP binding domain of Escherichia coli adenylate kinase. Biochemistry 35:6100–6106PubMedCrossRefGoogle Scholar
  5. Black ME, Hruby DE (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 PubMedGoogle Scholar
  6. Blight KJ, Kolyhalow AA, Reed KE, Agapow EV. Rice CM (1998) Molecular virology of hepatitis C virus an update with respect to potential antiviral targets. Antiviral Therapy 3 (Supplement 3) 71–81. Google Scholar
  7. Bochkarev A, Pfuetzner RA, Edwards AM, Frappier L (1997) Structure of single-stranded-DNA-binding domain of replication A protein bound to DNA. Nature 385:176–181PubMedCrossRefGoogle Scholar
  8. Bruckner RC, Crute JJ, Dodson MS, Lehman IR (1991) The herpes simplex virus 1 origin binding protein a DNA helicase. J Biol Chem 266:2669–2674PubMedGoogle Scholar
  9. Bryant GL, Harris MS, Baldwin ET, Tandeske L, Shoemaker KR, Finzel BC (1999) HCV helicase RNA-binding-domain flexibility quantified by comparison of multiple crystal forms. Annual American Crystallographic Association Meeting. Google Scholar
  10. Butkiewicz N, Wendel M, Zhang R, Jubin R, Pichardo J, Smith EB, Hart AM, Ingram R, Durkin J, Mui PW, Murray MG, Ramanathan L, Dasmahapatra B (1996) Enhancement of hepatitis C Virus NS3 proteinase activity by association with NS4A-specific synthetic peptides identification of sequence and critical residues of NS4A for the cofactor activity. Virology 225:328–338PubMedCrossRefGoogle Scholar
  11. Cho H-S, Ha N-C, Kang L-W, Chung KM, Back SH, Jang SK, Oh B-H (1998) Crystal structure of RNA helicase from genotype lb hepatitis C virus. J Biol Chem 273:15045–15052PubMedCrossRefGoogle Scholar
  12. Choo Q-L, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-born non-A, non-B viral hepatitis genome. Science 244:359–362PubMedCrossRefGoogle Scholar
  13. Choo Q-L, Richman KH, Han JH, Berger K, Lee C, Dong C, Gallegos C, Coit D, Medina-Selby A, Barr PJ, Weiner A J, Bradley DW, Kuo G, Houghton M (1991) Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci USA 88:2451–2455PubMedCrossRefGoogle Scholar
  14. Eagles RM, Balmori-Melian E, Beck DL, Gardner RC, Forster RLS (1994) Characterization of NTPase, RNA-binding and RNA-helicase activities of the cytoplasmic inclusion protein of tamarillo mosaic potyvirus. Eur J Biochem 224:677–684PubMedCrossRefGoogle Scholar
  15. Failla C, Tomei L, De Francesco R (1994) Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. J Virol 68:3753–3760PubMedGoogle Scholar
  16. Fernandez A, Garcia JA (1996) The RNA helicase CI from plum pox poty virus has two regions involved in binding to RNA. FEBS Letts 388:206–210CrossRefGoogle Scholar
  17. Gallinari P, Brennan D, Nardi C, Brunetti M, Tomei L, Steinkiihler C, De Francesco R (1998) Multiple enzymatic activities associated with recombinant NS3 protein of hepatitis C virus. J Virol 72:6758–6769PubMedGoogle Scholar
  18. Gorbalenya AE, Koonin EV (1993) Helicases amino acid sequence comparisons and structure-function relationships. Curr Opin Struc Biol 3:419–429CrossRefGoogle Scholar
  19. Gorbalenya AE, Koonin V, Donchenko AP, Blinov VM (1989) Two related superfamilies of putative helicases involved in replication recombination repair and expression of DNA and RNA genomes. Nucleic Acids Res 17:4713–729PubMedCrossRefGoogle Scholar
  20. Grakoui A, Wychowski C, Lin C, Feinstone SM, Rice CM (1993) Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol 67:1385–1395PubMedGoogle Scholar
  21. Gross CH, Shuman S (1996) The QRXGRXGRXXXR motif of the vaccinia virus DExH box RNA helicase NPH-II is required for ATP hydrolysis and RNA unwinding but not for RNA binding. J Virol 70:1706–1713PubMedGoogle Scholar
  22. Gwack Y, Kim DW, Han JH, Choe J (1996) Characterization of the RNA binding activity and RNA helicase activity of the hepatitis C virus NS3 protein. Biochem Biophys Res Com 225:654–659PubMedCrossRefGoogle Scholar
  23. Gwack Y, Kim DW, Han JH, Choe J (1997) DNA helicase activity of the hepatitis C virus nonstructural protein 3. Eur J Bioch 250:47–54CrossRefGoogle Scholar
  24. Hakansson K, Doherty AJ, Shuman S, Wigley DB (1997) X-ray crystallography reveals a large conformational change during guanyl transfer by mRNA capping enzymes. Cell 89:545–553PubMedCrossRefGoogle Scholar
  25. Hall MC, Matson SW (1997) Mutation of a highly conserved arginine in motif VI of Escherichia coli DNA helicase II results in an ATP-binding defect. J Biol Chem 272:18614–18620PubMedCrossRefGoogle Scholar
  26. Heilek GM, Peterson MG (1997) A point mutation abolishes the helicase but not the nucleoside triphosphatase activity of hepatitis C virus NS3 protein. J Virol 71:6264–6266PubMedGoogle Scholar
  27. Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Shimotohno K (1991) Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proc Natl Acad Sci USA 88:5547–5551PubMedCrossRefGoogle Scholar
  28. Hirling H, Scheffner M, Restle T, Stahl H (1989) RNA helicase activity associated with human p68 protein. Nature 339:562–564PubMedCrossRefGoogle Scholar
  29. Hong Z, Ferrari E, Wright-Minogue J, Chase R, Risano C, Seelig G, Lee C-G, Kwong AD (1996) Enzymatic characterization of hepatitis C virus NS3/4A complexes expressed in mammalian cells by using the herpes simplex virus amplicon system. J Virol 70:4261–4268PubMedGoogle Scholar
  30. Houghton M (1996) Hepatitis C viruses, In: Fields BN, Knipe DM, Howley PM (eds) Virology. Raven, New York, pp 1035–1058Google Scholar
  31. Hsu CC, Hwant L-H, Huang Y-W, Chi W-K, Chu Y-D, Chen D-S (1998) An ELISA for RNA helicase activity application as an assay of the NS3 helicase of hepatitis C virus. Biochem Biophys Res Com 253:594–599PubMedCrossRefGoogle Scholar
  32. Jin L, Peterson DL (1995) Expression isolation and characterization of the hepatitis C virus ATPase/RNA helicase. Arch Biochem Biophys 323:47–53PubMedCrossRefGoogle Scholar
  33. Jones PS (1998) Strategies for antiviral drug discovery. Antivir Chem and Chemother 9:283–302Google Scholar
  34. Kadare G, Haenni A-L (1997) Minireview: virus-encoded RNA helicases. J Virol 71:2583–2590PubMedGoogle Scholar
  35. Kaito M, Watanabe S, Tsukiyama-Kohara K, Yamaguchi K, Kobayashi Y, Konishi M, Yokoi M, Ishida S, Suzuki S, Kohara M (1994) Hepatitis C virus particle detected by immunoelectron microscopic study. J Gen Virol 75:1755–1760PubMedCrossRefGoogle Scholar
  36. Kanai A, Tanabe K, Kohara M (1995) Poly (U) binding activity of hepatitis C virus NS3 protein a putative RNA helicase. FEBS Letters 376:221–224PubMedCrossRefGoogle Scholar
  37. Kim DW, Gwack Y, Han JH, Choe J (1995) C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity. Biochem Biophys Res Comm 215:160–166PubMedCrossRefGoogle Scholar
  38. Kim DW, Gwack Y, Hang JH, Choe J (1997a) Towards defining a minimal functional domain for NTPase and RNA helicase activities of the hepatitis C virus NS3 protein. Virus Res 49:17–25PubMedCrossRefGoogle Scholar
  39. Kim JL, Caron PR (1998) Crystal structure of hepatitis C virus NS3 RNA helicase reveals a possible enzyme mechanism and suggests multiple potential drug binding sites. International Antiviral News 6:26–28Google Scholar
  40. Kim JL, Morgenstern KA, Griffith JP, Dwyer MD, Thomson JA, Murcko MA, Lin C, Caron PR (1998) Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding. Structure 6:89–100PubMedCrossRefGoogle Scholar
  41. Kim JL, Morgenstern KA, Lin C, Fox T, Dwyer MD, Landro JA, Chambers SP, Markland W, Lepre CA, O’Malley ET, Harbeson SL, Rice CM, Murcko MA, Caron PR, Thomson JA (1996) Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide. Cell 87:343–355PubMedCrossRefGoogle Scholar
  42. Kim DW, Kim J, Gwack Y, Han JH, Choe J (1997b) Mutational analysis of the hepatitis C virus RNA helicase. J Virol 71:9400–9409PubMedGoogle Scholar
  43. Kolykhalov A, Feinstone SM, Rice CM (1996) Identification of a highly conserved sequence element at the 3’terminus of hepatitis C virus genome RNA. J Virol 70:3363–3371PubMedGoogle Scholar
  44. Kolykhalov AA, Agapov EV, Blight KJ, Mihalik K, Feinstone S, Rice CM (1997) Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277:570–574PubMedCrossRefGoogle Scholar
  45. Korolev S, Hsieh J, Gauss GH, Lohman TM, Waksman G (1997) Major domain swiveling revealed by the crystal structures of complexes of E. coli Rep helicase bound to single-stranded DNA and ADP. Cell 90:635–647PubMedCrossRefGoogle Scholar
  46. Korolev S, Yao N, Lohman TM, Weber PC, Waksman G (1998) Comparison between the structures of HCV and Rep helicases reveal structural similarities between SF1 and SF2 super-families of helicases. Prot Sci 7:605–610CrossRefGoogle Scholar
  47. Kuo M-D, Chin C, Hsu S-L, Shiao J-Y, Wang T-M, Lin J-H (1996) Characterization of the NTPase activity of Japanese encephalitis virus NS3 protein. J Gen Virol 77:2077–2084PubMedCrossRefGoogle Scholar
  48. Kwong AD, Risano C (1998) Development of a hepatitis C virus RNA helicase high throughput assay, Chapter 9. In: Kinchington D, Schinazi RF (eds) Antiviral Methods and Protocols. Humana Press Inc, Totowa NJGoogle Scholar
  49. Kyono K, Miyashiro M, Taguchi I (1998) Detection of hepatitis C virus helicase activity using the scintillation proximity assay system. Anal Biochem 257:120–126PubMedCrossRefGoogle Scholar
  50. Lain S, Martin MT, Riechmann JL, Garcia JA (1991a) Novel catalytical activity associated with positivestrand RNA virus infection nucleic acid-stimulated ATPase activity of the plum pox potyvirus helicase-like protein. J Virol 65:1–6PubMedGoogle Scholar
  51. Lain S, Riechmann JL, Garcia JA (1991b) RNA helicase a novel activity associated with a protein encoded by a positive-strand RNA virus. Nucleic Acids Res 18:7003–7006CrossRefGoogle Scholar
  52. Landro JA, Raybuck SA, Luong Y-C, O’Malley ET, Harbeson SL, Morgenstern KA, Rao G, LivingstonDJ (1997) Mechanistic role of an NS4A peptide cofactor with the truncated ns3 protease of hepatitis 36:9340–9348. Google Scholar
  53. Laxton CD, McMillan D, Sullivan V, Ackrill AM (1998) Expression and characterization of the hepatitis G virus helicase. J Viral Hepatitis 5:21–26CrossRefGoogle Scholar
  54. Lee C-G, Hurwitz J (1992) A new RNA helicase isolated from HeLa cells that catalytically translocates in the 3’ to 5’ direction. J Biol Chem 267:4398–4407. Google Scholar
  55. Lin C, Lindenbach BD, Pragai BM, McCourt DW, Rice CM (1994) Processing in the hepatitis C virus E2-NS2 region identification of p7 and two distinct E2-specific products with dfferent C termini. J Virol 68:5063–5073PubMedGoogle Scholar
  56. Liuzzi M, Crute J, Grygon C, Hargrave K, Simoneau B, Faucher A, Bolger G, Duan J, Kibler P, Cordingley M (1998) Aminothiazolyl-phenyl-based inhibitors of HSV helicase-primase: a novel class of orally active antiherpetic agents. Antiviral Research 37:A42CrossRefGoogle Scholar
  57. Lohman TM, Bjornson KP (1996) Mechanisms of helicase-catalyzed DNA unwinding. Ann Rev Biochem 65:169–214PubMedCrossRefGoogle Scholar
  58. Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T, Hostomska Z (1996) The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. Cell 87:331–342PubMedCrossRefGoogle Scholar
  59. Markland W, Petrillo RA, Fitzgibbon M, Fox T, McCarrick R, McQuaid T, Fulghum JR, Chen W, Fleming MA, Thompson J A, Chambers SP (1997) Purification and characterization of the NS3 serine protease domain of hepatitis C virus expressed in Saccharomyces cerevisiae. J Gen Virology 78: 39–43Google Scholar
  60. Martinez R, Shao L, Weller SK (1992) The conserved helicase motifs of the herpes simples virus type-I origin bindng protein UL9 are important for function. J Virol 66:6735–6746PubMedGoogle Scholar
  61. Mastrangelo I A, Hough PVC, Wall JS, Dodson M, Dean FB, Hurwitz J (1989) ATP-dependent assembly double hexamers of SV40 T antigen at the viral origin of DNA replication. Nature 338:658–662PubMedCrossRefGoogle Scholar
  62. Miller RH, Purcell RH (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 USA 87:2057–2061PubMedCrossRefGoogle Scholar
  63. Morgenstern KA, Landro J A, Hsiao K, Lin C, Yong G, Su MS-S, Thomson J A (1997) Polynucleotide modulation of the protease nucleoside triphosphatase and helicase activities of a hepatitis C virus NS3-NS4A complex isolated from transfected COS Cells. J Virol 71:3767–3775PubMedGoogle Scholar
  64. Pai EF, Krengel U, Petsko GA, Gody RS, Katsch W, Wittinghofer A (1990) Refined crystal structure of the triphosphate conformation of H-ras p21 at 135A resoluton implications for the mechanism of GTP hydrolysis. EMBO J 9:2351–2359PubMedGoogle Scholar
  65. Pause A, Methot N, Sonenberg N (1993) The HRIGRXXR region of the DEAD box RNA helicase eukaryotic translation initiation factor 4A is required for RNA binding and ATP hydrolysis. Mol Cell Biol 13:6789–6798PubMedGoogle Scholar
  66. Preugschat F, Averett DR, Clarke BE, Porter DJT (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 271:24449–24457PubMedCrossRefGoogle Scholar
  67. Purcell RH (1994) Hepatitis C virus historical perspective and current concepts. FEMS Microbiol Rev 14:181–192PubMedCrossRefGoogle Scholar
  68. Raghunathan S, Ricard CS, Lohman TM, Waksman G (1997) Crystal structure of the homo-tetrameric DNA-binding domain of Escherichia coli single-stranded DNA-binding protein determined by mul- tiwavelength X-ray diffraction on the selenomethionyl protein at 2.9A resolution. Proc Natl Acad Sci USA 94:6652–6657PubMedCrossRefGoogle Scholar
  69. Reha-Krantz LJ, Hurwitz J (1978) The dnaB gene product of Escheriachia coli. I. Purification homogeneity and physical properties. J Biol Chem 253:4043–050Google Scholar
  70. Rice CM (1996) Flaviviridae the viruses and their replication. In: Fields BN, Knipe DM, Howley PM (eds) Virology. Raven, New York, pp 931–960Google Scholar
  71. Ruff M, Moras D (1991) Class II aminoacyl transfer RNA synthetases: crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNA(Asp). Science 252:1682–1689PubMedCrossRefGoogle Scholar
  72. Saraste M, Sibbald PR, Wittinghofer A (1990) The P-loop - a common motif in ATP- and GTP-binding proteins. Trends Biochem Sci 15:430–434PubMedCrossRefGoogle Scholar
  73. Scheffner M, Knippers R, Stahl H (1989) RNA unwinding activity of SV40 large T antigen Cell 57: 955–963. Google Scholar
  74. Schulz GE (1992) Induced-fit movement in adenylate kinases. Faraday Discuss 93:85–93PubMedCrossRefGoogle Scholar
  75. Seo YS, Lee SH, Hurwitz J (1991) Isolation of a DNA helicase from HeLa cells requiring the multisubunit human single-stranded DNA-binding protein for activity. J Biol Chem 266:13161–13170PubMedGoogle Scholar
  76. Shuman S (1993) Vaccinia virus RNA helicase directionality and substrate specificity. J Biol Chem 268:11798–11802PubMedGoogle Scholar
  77. Smith DH, Kotin RM (1998) The Rep52 gene product of adeno-associated virus is a DNA helicase with 3’-to-5’ polarity. J Virol 72:4874–4881PubMedGoogle Scholar
  78. Spector FC, Liang L, Giordano H, Sivaraja M, Peerson MG (1998a) T157602 a 2-amino-thiazole inhibits HSV replication by interacting with the UL5 component of the UL5/8/52 helicase primase complex. Antiviral Research 37:A43Google Scholar
  79. Spector FC, Liang L, Giordano H, Sivaraja M, Peterson MG (1998b) Inhibition of herpes simplex virus replication by a 2-amino thiazole via interactions with the helicase component of the UL5-UL8-UL52 complex. J Virol 72:6979–6987PubMedGoogle Scholar
  80. Steinkiihler C, Tomei L, De Francesco R (1996) In vitro activity of hepatitis C virus protease NS3 purified from recombinant baculovirus-infected Sf9 cells. J Biol Chem. 271:6367–6373CrossRefGoogle Scholar
  81. Subramanya HS, Bird LE, Brannigan JA, Wigley DB (1996) Crystal structure of a DExx box DNA Helicase. Nature 384:379–383PubMedCrossRefGoogle Scholar
  82. Suzich JA, Tamura JK, Palmer-Hill F, Warrener P, Grakoui A, Rice CM, Feinstone SM, Collett MS (1993) Hepatitis C virus NS3 protein polynucleotide-stimulated nucleoside triphosphatase and comparison with the related pestivirus and flavivirus enzymes. J Virol 67:6152–6158PubMedGoogle Scholar
  83. 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 70:8477–8484PubMedGoogle Scholar
  84. Takamizawa A, Mori C, Fuke I, Manabe S, Murakami S, Fujita J, Onishi E, Andoh T, Yoshida I, Okayama H (1991) Structure and organization of the hepatitis C virus genome isolated from human carrier. J Virol 65:1105–1113PubMedGoogle Scholar
  85. Tanaka T, Kato N, Cho M-J, Shimotohno K (1995) A novel sequence found at the 3’ terminus of hepatitis C virus genome. Biochem Biophys Res Commun 215:744–749. PubMedCrossRefGoogle Scholar
  86. Tanaka T, Kato N, Cho M-J, Sugiyama K, Shimotohno K (1996) Structure of the 3’ terminus of the hepatitis C virus genome. J Virol 70:3307–3312PubMedGoogle Scholar
  87. Tanji Y, Hijikata M, Satoh S, Kaneko T, Shimotohno K (1995) Hepatitits C virus-encoded nonstructural protein NS4A has versatile functions in viral protein processing. J Virol 69:1575–1581PubMedGoogle Scholar
  88. Walker JE MS, Runswick MJ, Gay NJ (1982) Distantly related sequences in the a- and b-subunits of ATP synthase myosin kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1:945–951PubMedGoogle Scholar
  89. Warrener P, Collett M (1995) Pestivirus NS3 (p80) protein possesses RNA helicase activity. J Virol 69:1720–1726PubMedGoogle Scholar
  90. Warrener P, Tamura JK, Collett MS (1993) RNA-stimulated NTPase activity associated with yellow fever virus NS3 protein expressed in bacteria. J Virol 67:989–996PubMedGoogle Scholar
  91. Weng Y, Czaplinski K, Peltz S (1996) Genetic and biochemical characterization of mutations in the ATPase and helicase regions of the Upfl protein. Mol Cell Biol 16:5477–5490PubMedGoogle Scholar
  92. Wengler G (1991) The carboxyl-terminal part of the NS3 protein of the West Nile flavivirus can be isolated as a soluble protein after proteolytic cleavage and represents an RNA-stimulated NTPase. Virology 184:707–715PubMedCrossRefGoogle Scholar
  93. Wong I, Chao K, Bujalowski W, Lohman TM (1992) DNA-induced dimerization of the Escherichia coli rep helicase. Allosteric effects of single-stranded and duplex DNA. J Biol Chem 267:7596–7610Google Scholar
  94. Wong I, Lohman TM (1992) Allosteric steric effects of nucleotide cofactors on Escherichia coli Rep helicase DNA binding. Science 256:350–355PubMedCrossRefGoogle Scholar
  95. Yamada N, Tanihara NK, Takada A, Yorihuzi T, Tsutsumi M, Shimomura H, Tsuji T, Date T (1996) Genetic organization and diversity of the 3’noncoding region of the hepatitis C virus. Virology 223:255–261PubMedCrossRefGoogle Scholar
  96. Yan HG, Tsai MD (1991) Mechanism of adenylate kinase. Demonstration of a functional relationship between aspartate 93 and Mg2 + by site-directed mutagenesis and proton phosphorus-31 and mag- nesium-25 NMR. Biochemistry 30:5539–5546PubMedCrossRefGoogle Scholar
  97. Yanagi M, Purcell RH, Emerson SU, Bukh J (1997) Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee. Proc Natl Acad Sci USA 94:8738–8743PubMedCrossRefGoogle Scholar
  98. Yanagi M, St Claire M, Shapiro M, Emerson SU, Purcell RH, Bukh J (1998) Transcripts of a chimeric cDNA clone of hepatitis C virus genotype lb are infectious in vivo. Virology 244:161–172PubMedCrossRefGoogle Scholar
  99. Yao N, Hesson T, Cable M, Hong Z, Kwong AD, Le HV, Weber PC (1997) Structure of the hepatitis C virus RNA helicase domain. Nature Structural Biology 4:463–167PubMedCrossRefGoogle Scholar
  100. Yao N, Weber PC (1998) Helicase a target for novel inhibitors of hepatitis C virus. Antiviral Therapy 3:93–97PubMedGoogle Scholar
  101. Zhang S, Grosse F (1994) Nuclear DNA helicase II unwinds both DNA and RNA. Biochemistry 33:3906–3912PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • A. D. Kwong
    • 1
  • J. L. Kim
    • 1
  • C. Lin
    • 1
  1. 1.Vertex Pharmaceuticals, Inc.CambridgeUSA

Personalised recommendations