Skip to main content
SpringerLink
Log in

Structure and Function of Hepatitis C Virus NS3 Helicase

  • Chapter
The Hepatitis C Viruses

Part of the book series: Current Topics in Microbiology and Immunology ((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).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bartenschlager R (1997) Candidate targets for hepatitis C virus-specific antiviral therapy. Intervirology 40:378–393

    Article  PubMed  CAS  Google Scholar 

  • 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 69:7519–7528

    PubMed  CAS  Google Scholar 

  • Bayliss CD, Smith GL (1996) Vaccinia virion protein 18R has both DNA and RNA helicase activities implications for vaccinia virus transcription. J Virol 70:794–800

    PubMed  CAS  Google Scholar 

  • Bilderback T, Fulmer T, Mantulin WW, Glaser M (1996) Substrate binding causes movement in the ATP binding domain of Escherichia coli adenylate kinase. Biochemistry 35:6100–6106

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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 

  • Bochkarev A, Pfuetzner RA, Edwards AM, Frappier L (1997) Structure of single-stranded-DNA-binding domain of replication A protein bound to DNA. Nature 385:176–181

    Article  PubMed  CAS  Google Scholar 

  • Bruckner RC, Crute JJ, Dodson MS, Lehman IR (1991) The herpes simplex virus 1 origin binding protein a DNA helicase. J Biol Chem 266:2669–2674

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 225:328–338

    Article  PubMed  CAS  Google Scholar 

  • 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 273:15045–15052

    Article  PubMed  CAS  Google Scholar 

  • 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 244:359–362

    Article  PubMed  CAS  Google Scholar 

  • 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 88:2451–2455

    Article  PubMed  CAS  Google Scholar 

  • 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 224:677–684

    Article  PubMed  CAS  Google Scholar 

  • 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 68:3753–3760

    PubMed  CAS  Google Scholar 

  • Fernandez A, Garcia JA (1996) The RNA helicase CI from plum pox poty virus has two regions involved in binding to RNA. FEBS Letts 388:206–210

    Article  CAS  Google Scholar 

  • 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 72:6758–6769

    PubMed  CAS  Google Scholar 

  • Gorbalenya AE, Koonin EV (1993) Helicases amino acid sequence comparisons and structure-function relationships. Curr Opin Struc Biol 3:419–429

    Article  CAS  Google Scholar 

  • 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 17:4713–729

    Article  PubMed  CAS  Google Scholar 

  • Grakoui A, Wychowski C, Lin C, Feinstone SM, Rice CM (1993) Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol 67:1385–1395

    PubMed  CAS  Google Scholar 

  • 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 70:1706–1713

    PubMed  CAS  Google Scholar 

  • 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 225:654–659

    Article  PubMed  CAS  Google Scholar 

  • Gwack Y, Kim DW, Han JH, Choe J (1997) DNA helicase activity of the hepatitis C virus nonstructural protein 3. Eur J Bioch 250:47–54

    Article  CAS  Google Scholar 

  • 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 89:545–553

    Article  PubMed  CAS  Google Scholar 

  • 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 272:18614–18620

    Article  PubMed  CAS  Google Scholar 

  • 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 71:6264–6266

    PubMed  CAS  Google Scholar 

  • 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 88:5547–5551

    Article  PubMed  CAS  Google Scholar 

  • Hirling H, Scheffner M, Restle T, Stahl H (1989) RNA helicase activity associated with human p68 protein. Nature 339:562–564

    Article  PubMed  CAS  Google Scholar 

  • 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 70:4261–4268

    PubMed  CAS  Google Scholar 

  • Houghton M (1996) Hepatitis C viruses, In: Fields BN, Knipe DM, Howley PM (eds) Virology. Raven, New York, pp 1035–1058

    Google Scholar 

  • 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 253:594–599

    Article  PubMed  CAS  Google Scholar 

  • Jin L, Peterson DL (1995) Expression isolation and characterization of the hepatitis C virus ATPase/RNA helicase. Arch Biochem Biophys 323:47–53

    Article  PubMed  CAS  Google Scholar 

  • Jones PS (1998) Strategies for antiviral drug discovery. Antivir Chem and Chemother 9:283–302

    CAS  Google Scholar 

  • Kadare G, Haenni A-L (1997) Minireview: virus-encoded RNA helicases. J Virol 71:2583–2590

    PubMed  CAS  Google Scholar 

  • 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 75:1755–1760

    Article  PubMed  CAS  Google Scholar 

  • Kanai A, Tanabe K, Kohara M (1995) Poly (U) binding activity of hepatitis C virus NS3 protein a putative RNA helicase. FEBS Letters 376:221–224

    Article  PubMed  CAS  Google Scholar 

  • 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 215:160–166

    Article  PubMed  CAS  Google Scholar 

  • 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 49:17–25

    Article  PubMed  CAS  Google Scholar 

  • 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 6:26–28

    Google Scholar 

  • 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 6:89–100

    Article  PubMed  CAS  Google Scholar 

  • 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 87:343–355

    Article  PubMed  CAS  Google Scholar 

  • Kim DW, Kim J, Gwack Y, Han JH, Choe J (1997b) Mutational analysis of the hepatitis C virus RNA helicase. J Virol 71:9400–9409

    PubMed  CAS  Google Scholar 

  • 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 70:3363–3371

    PubMed  CAS  Google Scholar 

  • Kolykhalov AA, Agapov EV, Blight KJ, Mihalik K, Feinstone S, Rice CM (1997) Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277:570–574

    Article  PubMed  CAS  Google Scholar 

  • 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 90:635–647

    Article  PubMed  CAS  Google Scholar 

  • 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 7:605–610

    Article  CAS  Google Scholar 

  • 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 77:2077–2084

    Article  PubMed  CAS  Google Scholar 

  • 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 NJ

    Google Scholar 

  • Kyono K, Miyashiro M, Taguchi I (1998) Detection of hepatitis C virus helicase activity using the scintillation proximity assay system. Anal Biochem 257:120–126

    Article  PubMed  CAS  Google Scholar 

  • 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 65:1–6

    PubMed  CAS  Google Scholar 

  • 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 18:7003–7006

    Article  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • Laxton CD, McMillan D, Sullivan V, Ackrill AM (1998) Expression and characterization of the hepatitis G virus helicase. J Viral Hepatitis 5:21–26

    Article  CAS  Google Scholar 

  • 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 

  • 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 68:5063–5073

    PubMed  CAS  Google Scholar 

  • 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:A42

    Article  Google Scholar 

  • Lohman TM, Bjornson KP (1996) Mechanisms of helicase-catalyzed DNA unwinding. Ann Rev Biochem 65:169–214

    Article  PubMed  CAS  Google Scholar 

  • 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 87:331–342

    Article  PubMed  CAS  Google Scholar 

  • 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: 39–43

    CAS  Google Scholar 

  • 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 66:6735–6746

    PubMed  CAS  Google Scholar 

  • 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 338:658–662

    Article  PubMed  CAS  Google Scholar 

  • 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 87:2057–2061

    Article  PubMed  CAS  Google Scholar 

  • 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 71:3767–3775

    PubMed  CAS  Google Scholar 

  • 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 9:2351–2359

    PubMed  CAS  Google Scholar 

  • 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 13:6789–6798

    PubMed  CAS  Google Scholar 

  • 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 271:24449–24457

    Article  PubMed  CAS  Google Scholar 

  • Purcell RH (1994) Hepatitis C virus historical perspective and current concepts. FEMS Microbiol Rev 14:181–192

    Article  PubMed  CAS  Google Scholar 

  • 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 94:6652–6657

    Article  PubMed  CAS  Google Scholar 

  • Reha-Krantz LJ, Hurwitz J (1978) The dnaB gene product of Escheriachia coli. I. Purification homogeneity and physical properties. J Biol Chem 253:4043–050

    CAS  Google Scholar 

  • Rice CM (1996) Flaviviridae the viruses and their replication. In: Fields BN, Knipe DM, Howley PM (eds) Virology. Raven, New York, pp 931–960

    Google Scholar 

  • Ruff M, Moras D (1991) Class II aminoacyl transfer RNA synthetases: crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNA(Asp). Science 252:1682–1689

    Article  PubMed  CAS  Google Scholar 

  • Saraste M, Sibbald PR, Wittinghofer A (1990) The P-loop - a common motif in ATP- and GTP-binding proteins. Trends Biochem Sci 15:430–434

    Article  PubMed  Google Scholar 

  • Scheffner M, Knippers R, Stahl H (1989) RNA unwinding activity of SV40 large T antigen Cell 57: 955–963.

    CAS  Google Scholar 

  • Schulz GE (1992) Induced-fit movement in adenylate kinases. Faraday Discuss 93:85–93

    Article  PubMed  CAS  Google Scholar 

  • 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 266:13161–13170

    PubMed  CAS  Google Scholar 

  • Shuman S (1993) Vaccinia virus RNA helicase directionality and substrate specificity. J Biol Chem 268:11798–11802

    PubMed  CAS  Google Scholar 

  • Smith DH, Kotin RM (1998) The Rep52 gene product of adeno-associated virus is a DNA helicase with 3’-to-5’ polarity. J Virol 72:4874–4881

    PubMed  CAS  Google Scholar 

  • 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:A43

    Google Scholar 

  • 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 72:6979–6987

    PubMed  CAS  Google Scholar 

  • 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. 271:6367–6373

    Article  Google Scholar 

  • Subramanya HS, Bird LE, Brannigan JA, Wigley DB (1996) Crystal structure of a DExx box DNA Helicase. Nature 384:379–383

    Article  PubMed  CAS  Google Scholar 

  • 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 67:6152–6158

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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 65:1105–1113

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 70:3307–3312

    PubMed  CAS  Google Scholar 

  • 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 69:1575–1581

    PubMed  CAS  Google Scholar 

  • 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 1:945–951

    PubMed  CAS  Google Scholar 

  • Warrener P, Collett M (1995) Pestivirus NS3 (p80) protein possesses RNA helicase activity. J Virol 69:1720–1726

    PubMed  CAS  Google Scholar 

  • Warrener P, Tamura JK, Collett MS (1993) RNA-stimulated NTPase activity associated with yellow fever virus NS3 protein expressed in bacteria. J Virol 67:989–996

    PubMed  CAS  Google Scholar 

  • 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 16:5477–5490

    PubMed  CAS  Google Scholar 

  • 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 184:707–715

    Article  PubMed  CAS  Google Scholar 

  • 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 267:7596–7610

    CAS  Google Scholar 

  • Wong I, Lohman TM (1992) Allosteric steric effects of nucleotide cofactors on Escherichia coli Rep helicase DNA binding. Science 256:350–355

    Article  PubMed  CAS  Google Scholar 

  • 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 223:255–261

    Article  PubMed  CAS  Google Scholar 

  • 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 30:5539–5546

    Article  PubMed  CAS  Google Scholar 

  • 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 94:8738–8743

    Article  PubMed  CAS  Google Scholar 

  • 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 244:161–172

    Article  PubMed  CAS  Google Scholar 

  • 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 4:463–167

    Article  PubMed  CAS  Google Scholar 

  • Yao N, Weber PC (1998) Helicase a target for novel inhibitors of hepatitis C virus. Antiviral Therapy 3:93–97

    PubMed  CAS  Google Scholar 

  • Zhang S, Grosse F (1994) Nuclear DNA helicase II unwinds both DNA and RNA. Biochemistry 33:3906–3912

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vertex Pharmaceuticals, Inc., 130 Waverly Street, Cambridge, MA, 02139, USA

    A. D. Kwong, J. L. Kim & C. Lin

Authors
  1. A. D. Kwong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. L. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Digestive Diseases and Genetics — Winship Cancer Center, Emory University School of Medicine, 1639 Pierce Drive, Rm 2101 WMRB, 30322, Atlanta, GA, USA

    Curt H. Hagedorn M.D.

  2. Department of Molecular Microbiology, Washington University School of Medicine, 600 South Euclid Avenue, 63110, St. Louis, MO, USA

    Charles M. Rice M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kwong, A.D., Kim, J.L., Lin, C. (2000). Structure and Function of Hepatitis C Virus NS3 Helicase. In: Hagedorn, C.H., Rice, C.M. (eds) The Hepatitis C Viruses. Current Topics in Microbiology and Immunology, vol 242. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59605-6_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-59605-6_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64047-6

  • Online ISBN: 978-3-642-59605-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation