Advertisement

Structure-Function Relationships Among RNA-Dependent RNA Polymerases

  • Kenneth K.-S. Ng
  • Jamie J. Arnold
  • Craig E. Cameron
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 320)

Abstract

RNA-dependent RNA polymerases (RdRPs) play key roles in viral transcription and genome replication, as well as epigenetic and post-transcriptional control of cellular gene expression. In this article, we review the crystallographic, biochemical, and molecular genetic data available for viral RdRPs that have led to a detailed description of substrate and cofactor binding, fidelity of nucleotide selection and incorporation, and catalysis. It is likely that the cellular RdRPs will share some of the basic structural and mechanistic principles gleaned from studies of viral RdRPs. Therefore, studies of the viral RdRP establish a framework for the study of cellular RdRPs, an important yet understudied class of nucleic acid polymerases.

Keywords

Bovine Viral Diarrhea Virus Rabbit Hemorrhagic Disease Virus Elongation Complex Feline Calicivirus RdRP Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ago H, Adachi T, Yoshida A, Yamamoto M, Habuka N, Yatsunami K, Miyano M (1999) Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Structure Fold Des 7:1417–1426.PubMedCrossRefGoogle Scholar
  2. Andino R, Rieckhof GE, Baltimore D (1990) A functional ribonucleoprotein complex forms around the 5n end of poliovirus RNA. Cell 63:369–380.PubMedCrossRefGoogle Scholar
  3. Andino R, Rieckhof GE, Achacoso PL, Baltimore D (1993) Poliovirus RNA synthesis utilizes an RNP complex formed around the 5A-end of viral RNA. EMBO J 12:3587–3598.PubMedGoogle Scholar
  4. Andino R, Boddeker N, Silvera D, Gamarnik AV (1999) Intracellular determinants of picornavirus replication. Trends Microbiol 7:76–82.PubMedCrossRefGoogle Scholar
  5. Appleby TC, Luecke H, Shim JH, Wu JZ, Cheney IW, Zhong W, Vogeley L, Hong Z, Yao N (2005) Crystal structure of complete rhinovirus RNA polymerase suggests front loading of protein primer. J Virol 79:277–288.PubMedCrossRefGoogle Scholar
  6. Arnold JJ, Cameron CE (2000) Poliovirus RNA-dependent RNA polymerase [3D(pol)]. Assembly of stable, elongation-competent complexes by using a symmetrical primer-template substrate (sym/sub). J Biol Chem 275:5329–5336.PubMedCrossRefGoogle Scholar
  7. Arnold JJ, Cameron CE (2004) Poliovirus RNA-dependent RNA polymerase (3Dpol): pre-steady-state kinetic analysis of ribonucleotide incorporation in the presence of Mg2+. Biochemistry 43:5126–5137.PubMedCrossRefGoogle Scholar
  8. Arnold JJ, Ghosh SK, Cameron CE (1999) Poliovirus RNA-dependent RNA polymerase [3D(pol)]. Divalent cation modulation of primer, template, and nucleotide selection. J Biol Chem 274:37060–37069.PubMedCrossRefGoogle Scholar
  9. Arnold JJ, Gohara DW, Cameron CE (2004) Poliovirus RNA-dependent RNA polymerase (3Dpol): pre-steady-state kinetic analysis of ribonucleotide incorporation in the presence of Mn2+. Biochemistry 43:5138–5148.PubMedCrossRefGoogle Scholar
  10. Astier-Manifacier S, Cornuet P (1971) RNA-dependent RNA polymerase in Chinese cabbage. Biochim Biophys Acta 232:484–493.PubMedGoogle Scholar
  11. Astier-Manifacier S, Cornuet P (1978) Purification and molecular weight of an RNA-dependant RNA polymerase from Brassicae oleracea var. Botrytis (in French). C R Acad Sci Hebd Seances Acad Sci D 287:1043–1046.PubMedGoogle Scholar
  12. Belliot G, Sosnovtsev SV, Mitra T, Hammer C, Garfield M, Green KY (2003) In vitro proteolytic processing of the MD145 norovirus ORF1 nonstructural polyprotein yields stable precursors and products similar to those detected in calicivirus-infected cells. J Virol 77:10957–10974.PubMedCrossRefGoogle Scholar
  13. Belliot G, Sosnovtsev SV, Chang KO, Babu V, Uche U, Arnold JJ, Cameron CE, Green KY (2005) Norovirus proteinase-polymerase and polymerase are both active forms of RNA-dependent RNA polymerase. J Virol 79:2393–2403.PubMedCrossRefGoogle Scholar
  14. Biswal BK, Cherney MM, Wang M, Chan L, Yannopoulos CG, Bilimoria D, Nicolas O, Bedard J, James MN (2005) Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus reveal two conformations and suggest mechanisms of inhibition by non-nucleoside inhibitors. J Biol Chem 280:18202–18210.PubMedCrossRefGoogle Scholar
  15. Biswal BK, Wang M, Cherney MM, Chan L, Yannopoulos CG, Bilimoria D, Bedard J, James MN (2006) Non-nucleoside inhibitors binding to hepatitis C virus NS5B polymerase reveal a novel mechanism of inhibition. J Mol Biol 361:33–45.PubMedCrossRefGoogle Scholar
  16. Boege F, Sänger HL (1980) RNA-dependent RNA polymerase from healthy tomato leaf tissue. FEBS Lett 121:91–96.CrossRefGoogle Scholar
  17. Boerner JE, Lyle JM, Daijogo S, Semler BL, Schultz SC, Kirkegaard K, Richards OC (2005) Allosteric effects of ligands and mutations on poliovirus RNA-dependent RNA polymerase. J Virol 79:7803–7811.PubMedCrossRefGoogle Scholar
  18. Bressanelli S, Tomei L, Roussel A, Incitti I, Vitale RL, Mathieu M, De Francesco R, Rey FA (1999) Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc Natl Acad Sci U S A 96:13034–13039.PubMedCrossRefGoogle Scholar
  19. Bressanelli S, Tomei L, Rey FA, De Francesco R (2002) Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides. J Virol 76:3482–3492.PubMedCrossRefGoogle Scholar
  20. Bruenn JA (2003) A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases. Nucleic Acids Res 31:1821–1829.PubMedCrossRefGoogle Scholar
  21. Butcher SJ, Grimes JM, Makeyev EV, Bamford DH, Stuart DI (2001) A mechanism for initiating RNA-dependent RNA polymerization. Nature 410:235–240.PubMedCrossRefGoogle Scholar
  22. Cai Z, Yi M, Zhang C, Luo G (2005) Mutagenesis analysis of the rGTP-specific binding site of hepatitis C virus RNA-dependent RNA polymerase. J Virol 79:11607–11617.PubMedCrossRefGoogle Scholar
  23. Castro C, Arnold JJ, Cameron CE (2005) Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective. Virus Res 107:141–149.PubMedCrossRefGoogle Scholar
  24. Choi KH, Groarke JM, Young DC, Kuhn RJ, Smith JL, Pevear DC, Rossmann MG (2004) The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation. Proc Natl Acad Sci U S A 101:4425–4430.PubMedCrossRefGoogle Scholar
  25. Choi KH, Gallei A, Becher P, Rossmann MG (2006) The structure of bovine viral diarrhea virus RNA-dependent RNA polymerase and its amino-terminal domain. Structure 14:1107–1113.PubMedCrossRefGoogle Scholar
  26. Cogoni C, Macino G (1999) Gene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature 399:166–169.PubMedCrossRefGoogle Scholar
  27. Cornell CT, Semler BL (2002) Subdomain specific functions of the RNA polymerase region of poliovirus 3CD polypeptide. Virology 298:200–213.PubMedCrossRefGoogle Scholar
  28. Dhanak D, Duffy KJ, Johnston VK, Lin-Goerke J, Darcy M, Shaw AN, Gu B, Silverman C, Gates AT, Nonnemacher MR, Earnshaw DL, Casper DJ, Kaura A, Baker A, Greenwood C, Gutshall LL, Maley D, DelVecchio A, Macarron R, Hofmann GA, Alnoah Z, Cheng HY, Chan G, Khandekar S, Keenan RM, Sarisky RT (2002) Identification and biological characterization of heterocyclic inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem 277:38322–38327.PubMedCrossRefGoogle Scholar
  29. Di Marco S, Volpari C, Tomei L, Altamura S, Harper S, Narjes F, Koch U, Rowley M, De Francesco R, Migliaccio G, Carfi A (2005) Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site. J Biol Chem 280:29765–29770.PubMedCrossRefGoogle Scholar
  30. Doublie S, Ellenberger T (1998) The mechanism of action of T7 DNA polymerase. Curr Opin Struct Biol 8:704–712.PubMedCrossRefGoogle Scholar
  31. Doublie S, Tabor S, Long AM, Richardson CC, Ellenberger T (1998) Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution. Nature 391:251–258.PubMedCrossRefGoogle Scholar
  32. Doublie S, Sawaya MR, Ellenberger T (1999) An open and closed case for all polymerases. Structure 7:R31–R35.PubMedCrossRefGoogle Scholar
  33. Duda CT, Zaitlin M, Siegel A (1973) In vitro synthesis of double-stranded RNA by an enzyme system isolated from tobacco leaves. Biochim Biophys Acta 319:62–71.PubMedGoogle Scholar
  34. Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N (2004) Structure of foot-and-mouth disease virus RNA-dependent RNA polymerase and its complex with a template-primer RNA. J Biol Chem 279:47212–47221.PubMedCrossRefGoogle Scholar
  35. Ferrer-Orta C, Arias A, Agudo R, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N (2006) The structure of a protein primer-polymerase complex in the initiation of genome replication. EMBO J 25:880–888.PubMedCrossRefGoogle Scholar
  36. Flanegan JB, Baltimore D (1977) Poliovirus-specific primer-dependent RNA polymerase able to copy poly(A). Proc Natl Acad Sci U S A 74:3677–3680.PubMedCrossRefGoogle Scholar
  37. Franklin MC, Wang J, Steitz TA (2001) Structure of the replicating complex of a pol alpha family DNA polymerase. Cell 105:657–667.PubMedCrossRefGoogle Scholar
  38. Gohara DW, Crotty S, Arnold JJ, Yoder JD, Andino R, Cameron CE (2000) Poliovirus RNA-dependent RNA polymerase (3Dpol): structural, biochemical, and biological analysis of conserved structural motifs A and B. J Biol Chem 275:25523–25532.PubMedCrossRefGoogle Scholar
  39. Gohara DW, Arnold JJ, Cameron CE (2004) Poliovirus RNA-dependent RNA polymerase (3Dpol): kinetic, thermodynamic, and structural analysis of ribonucleotide selection. Biochemistry 43:5149–5158.PubMedCrossRefGoogle Scholar
  40. Gopalsamy A, Chopra R, Lim K, Ciszewski G, Shi M, Curran KJ, Sukits SF, Svenson K, Bard J, Ellingboe JW, Agarwal A, Krishnamurthy G, Howe AY, Orlowski M, Feld B, OGConnell J, Mansour TS (2006) Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site. J Med Chem 49:3052–3055.PubMedCrossRefGoogle Scholar
  41. Hansen JL, Long AM, Schultz SC (1997) Structure of the RNA-dependent RNA polymerase of poliovirus. Structure 5:1109–1122.PubMedCrossRefGoogle Scholar
  42. Harper S, Avolio S, Pacini B, Di Filippo M, Altamura S, Tomei L, Paonessa G, Di Marco S, Carfi A, Giuliano C, Padron J, Bonelli F, Migliaccio G, De Francesco R, Laufer R, Rowley M, Narjes F (2005) Potent inhibitors of subgenomic hepatitis C virus RNA replication through optimization of indole-N-acetamide allosteric inhibitors of the viral NS5B polymerase. J Med Chem 48:4547–4557.PubMedCrossRefGoogle Scholar
  43. Huang L, Gledhill J, Cameron CE (2003) RNA-dependent RNA polymerase in gene silencing. In: Hannon GJ (ed) RNAi: a guide to gene silencing. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 175–203.Google Scholar
  44. Jablonski SA, Morrow CD (1995) Mutation of the aspartic acid residues of the GDD sequence motif of poliovirus RNA-dependent RNA polymerase results in enzymes with altered metal ion requirements for activity. J Virol 69:1532–1539.PubMedGoogle Scholar
  45. Johnson SJ, Taylor JS, Beese LS (2003) Processive DNA synthesis observed in a polymerase crystal suggests a mechanism for the prevention of frameshift mutations. Proc Natl Acad Sci U S A 100:3895–3900.PubMedCrossRefGoogle Scholar
  46. Kaiser WJ, Chaudhry Y, Sosnovtsev SV, Goodfellow IG (2006) Analysis of protein-protein interactions in the feline calicivirus replication complex. J Gen Virol 87:363–368.PubMedCrossRefGoogle Scholar
  47. Kamer G, Argos P (1984) Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses. Nucleic Acids Res 12:7269–7282.PubMedCrossRefGoogle Scholar
  48. Laurila MR, Salgado PS, Makeyev EV, Nettelship J, Stuart DI, Grimes JM, Bamford DH (2005a) Gene silencing pathway RNA-dependent RNA polymerase of Neurospora crassa: yeast expression and crystallization of selenomethionated QDE-1 protein. J Struct Biol 149:111–115.PubMedCrossRefGoogle Scholar
  49. Laurila MR, Salgado PS, Stuart DI, Grimes JM, Bamford DH (2005b) Back-priming mode of phi6 RNA-dependent RNA polymerase. J Gen Virol 86:521–526.PubMedCrossRefGoogle Scholar
  50. Lee YF, Nomoto A, Detjen BM, Wimmer E (1977) A protein covalently linked to poliovirus genome RNA. Proc Natl Acad Sci U S A 74:59–63.PubMedCrossRefGoogle Scholar
  51. Lesburg CA, Cable MB, Ferrari E, Hong Z, Mannarino AF, Weber PC (1999) Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol 6:937–943.PubMedCrossRefGoogle Scholar
  52. Liu J, Tsai MD (2001) DNA polymerase beta: pre-steady-state kinetic analyses of dATP alpha S stereoselectivity and alteration of the stereoselectivity by various metal ions and by site-directed mutagenesis. Biochemistry 40:9014–9022.PubMedCrossRefGoogle Scholar
  53. Love RA, Parge HE, Yu X, Hickey MJ, Diehl W, Gao J, Wriggers H, Ekker A, Wang L, Thomson JA, Dragovich PS, Fuhrman SA (2003) Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme. J Virol 77:7575–7581.PubMedCrossRefGoogle Scholar
  54. Love RA, Maegley KA, Yu X, Ferre RA, Lingardo LK, Diehl W, Parge HE, Dragovich PS, Fuhrman SA (2004) The crystal structure of the RNA-dependent RNA polymerase from human rhinovirus: a dual function target for common cold antiviral therapy. Structure 12:1533–1544.PubMedCrossRefGoogle Scholar
  55. Lyle JM, Clewell A, Richmond K, Richards OC, Hope DA, Schultz SC, Kirkegaard K (2002) Similar structural basis for membrane localization and protein priming by an RNA-dependent RNA polymerase. J Biol Chem 277:16324–16331.PubMedCrossRefGoogle Scholar
  56. Makeyev EV, Bamford DH (2002) Cellular RNA-dependent RNA polymerase involved in posttranscriptional gene silencing has two distinct activity modes. Mol Cell 10:1417–1427.PubMedCrossRefGoogle Scholar
  57. Martin CT, Coleman JE (1989) T7 RNA polymerase does not interact with the 5M-phosphate of the initiating nucleotide. Biochemistry 28:2760–2762.PubMedCrossRefGoogle Scholar
  58. Mourrain P, Beclin C, Elmayan T, Feuerbach F, Godon C, Morel JB, Jouette D, Lacombe AM, Nikic S, Picault N, Remoue K, Sanial M, Vo TA, Vaucheret H (2000) Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 101:533–542.PubMedCrossRefGoogle Scholar
  59. Ng KK, Cherney MM, Vazquez AL, Machin A, Alonso JM, Parra F, James MN (2002) Crystal structures of active and inactive conformations of a caliciviral RNA-dependent RNA polymerase. J Biol Chem 277:1381–1387.PubMedCrossRefGoogle Scholar
  60. Ng KK, Pendas-Franco N, Rojo J, Boga JA, Machin A, Alonso JM, Parra F (2004) Crystal structure of Norwalk virus polymerase reveals the carboxyl terminus in the active site cleft. J Biol Chem 279:16638–16645.PubMedCrossRefGoogle Scholar
  61. Nishikura K (2001) A short primer on RNAi: RNA-directed RNA polymerase acts as a key catalyst. Cell 107:415–418.PubMedCrossRefGoogle Scholar
  62. Nomoto A, Detjen B, Pozzatti R, Wimmer E (1977) The location of the polio genome protein in viral RNAs and its implication for RNA synthesis. Nature 268:208–213.PubMedCrossRefGoogle Scholar
  63. O’Farrell D, Trowbridge R, Rowlands D, Jager J (2003) Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation. J Mol Biol 326:1025–1035.PubMedCrossRefGoogle Scholar
  64. O’Reilly EK, Kao CC (1998) Analysis of RNA-dependent RNA polymerase structure and function as guided by known polymerase structures and computer predictions of secondary structure. Virology 252:287–303.PubMedCrossRefGoogle Scholar
  65. Olsen DB, Benseler F, Cole JL, Stahlhut MW, Dempski RE, Darke PL, Kuo LC (1996) Elucidation of basic mechanistic and kinetic properties of influenza endonuclease using chemically synthesized RNAs. J Biol Chem 271:7435–7439.PubMedCrossRefGoogle Scholar
  66. Ortin J, Parra F (2006) Structure and function of RNA replication. Annu Rev Microbiol 60:305–326.PubMedCrossRefGoogle Scholar
  67. Parsley TB, Cornell CT, Semler BL (1999) Modulation of the RNA binding and protein processing activities of poliovirus polypeptide 3CD by the viral RNA polymerase domain. J Biol Chem 274:12867–12876.PubMedCrossRefGoogle Scholar
  68. Pathak HB, Ghosh SK, Roberts AW, Sharma SD, Yoder JD, Arnold JJ, Gohara DW, Barton DJ, Paul AV, Cameron CE (2002) Structure-function relationships of the RNA-dependent RNA polymerase from poliovirus (3Dpol). A surface of the primary oligomerization domain functions in capsid precursor processing and VPg uridylylation. J Biol Chem 277:31551–31562.PubMedCrossRefGoogle Scholar
  69. Paul AV, van Boom JH, Filippov D, Wimmer E (1998) Protein-primed RNA synthesis by purified poliovirus RNA polymerase. Nature 393:280–284.PubMedCrossRefGoogle Scholar
  70. Paul AV, Peters J, Mugavero J, Yin J, van Boom JH, Wimmer E (2003) Biochemical and genetic studies of the VPg uridylylation reaction catalyzed by the RNA polymerase of poliovirus. J Virol 77:891–904.PubMedCrossRefGoogle Scholar
  71. Pfefferkorn JA, Greene ML, Nugent RA, Gross RJ, Mitchell MA, Finzel BC, Harris MS, Wells PA, Shelly JA, Anstadt RA, Kilkuskie RE, Kopta LA, Schwende FJ (2005a) Inhibitors of HCV NS5B polymerase. Part 1. Evaluation of the southern region of (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl) acrylic acid. Bioorg Med Chem Lett 15:2481–2486.PubMedCrossRefGoogle Scholar
  72. Pfefferkorn JA, Nugent R, Gross RJ, Greene M, Mitchell MA, Reding MT, Funk LA, Anderson R, Wells PA, Shelly JA, Anstadt R, Finzel BC, Harris MS, Kilkuskie RE, Kopta LA, Schwende FJ (2005b) Inhibitors of HCV NS5B polymerase. Part 2. Evaluation of the northern region of (2Z)-2-benzoylamino-3-(4-phenoxy-phenyl)-acrylic acid. Bioorg Med Chem Lett 15:2812–2818.PubMedCrossRefGoogle Scholar
  73. Powers JP, Piper DE, Li Y, Mayorga V, Anzola J, Chen JM, Jaen JC, Lee G, Liu J, Peterson MG, Tonn GR, Ye Q, Walker NP, Wang Z (2006) SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA polymerase. J Med Chem 49:1034–1046.PubMedCrossRefGoogle Scholar
  74. Rothwell PJ, Waksman G (2005) Structure and mechanism of DNA polymerases. Adv Protein Chem 71:401–440.PubMedCrossRefGoogle Scholar
  75. Salgado PS, Makeyev EV, Butcher SJ, Bamford DH, Stuart DI, Grimes JM (2004) The structural basis for RNA specificity and Ca2+ inhibition of an RNA-dependent RNA polymerase. Structure 12:307–316.PubMedGoogle Scholar
  76. Salgado P, Koivunen MRL, Makeyev EV, Bamford DH, Stuart DI, Grimes JM (2006) The structure of an RNAi polymerase links RNA silencing and transcription, PLoS Biology 4(12):e434.PubMedCrossRefGoogle Scholar
  77. Sawaya MR, Prasad R, Wilson SH, Kraut J, Pelletier H (1997) Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: evidence for an induced fit mechanism. Biochemistry 36:11205–11215.PubMedCrossRefGoogle Scholar
  78. Schiebel W, Pelissier T, Riedel L, Thalmeir S, Schiebel R, Kempe D, Lottspeich F, Sanger HL, Wassenegger M (1998) Isolation of an RNA-directed RNA polymerase-specific cDNA clone from tomato. Plant Cell 10:2087–2101.PubMedCrossRefGoogle Scholar
  79. Sijen T, Fleenor J, Simmer F, Thijssen KL, Parrish S, Timmons L, Plasterk RH, Fire A (2001) On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107:465–476.PubMedCrossRefGoogle Scholar
  80. Smardon A, Spoerke JM, Stacey SC, Klein ME, Mackin N, Maine EM (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Curr Biol 10:169–178.PubMedCrossRefGoogle Scholar
  81. Sosnovtseva SA, Sosnovtsev SV, Green KY (1999) Mapping of the feline calicivirus proteinase responsible for autocatalytic processing of the nonstructural polyprotein and identification of a stable proteinase-polymerase precursor protein. J Virol 73:6626–6633.PubMedGoogle Scholar
  82. Steitz TA (1993) DNA- and RNA-dependent DNA polymerases. Curr Opin Struct Biol 3:31–38.CrossRefGoogle Scholar
  83. Steitz TA (1998) A mechanism for all polymerases. Nature 391:231–232.PubMedCrossRefGoogle Scholar
  84. Tao Y, Farsetta DL, Nibert ML, Harrison SC (2002) RNA synthesis in a cage-structural studies of reovirus polymerase lambda3. Cell 111:733–745.PubMedCrossRefGoogle Scholar
  85. Thompson AA, Peersen OB (2004) Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase. EMBO J 23:3462–3471.PubMedCrossRefGoogle Scholar
  86. Tomei L, Altamura S, Bartholomew L, Biroccio A, Ceccacci A, Pacini L, Narjes F, Gennari N, Bisbocci M, Incitti I, Orsatti L, Harper S, Stansfield I, Rowley M, De Francesco R, Migliaccio G (2003) Mechanism of action and antiviral activity of benzimidazole-based allosteric inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Virol 77:13225–13231.PubMedCrossRefGoogle Scholar
  87. van Dijk AA, Makeyev EV, Bamford DH (2004) Initiation of viral RNA-dependent RNA polymerization. J Gen Virol 85:1077–1093.PubMedCrossRefGoogle Scholar
  88. Vazquez AL, Alonso JM, Parra F (2000) Mutation analysis of the GDD sequence motif of a calicivirus RNA-dependent RNA polymerase. J Virol 74:3888–3891.PubMedCrossRefGoogle Scholar
  89. Wang M, Ng KK, Cherney MM, Chan L, Yannopoulos CG, Bedard J, Morin N, Nguyen-Ba N, Bethell RC, James MN (2003) Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase: crystal structures and mechanism of inhibition. J Biol Chem 278:9489–9495.PubMedCrossRefGoogle Scholar
  90. Wei L, Huhn JS, Mory A, Pathak HB, Sosnovtsev SV, Green KY, Cameron CE (2001) Proteinase-polymerase precursor as the active form of feline calicivirus RNA-dependent RNA polymerase. J Virol 75:1211–1219.PubMedCrossRefGoogle Scholar
  91. Yin YW, Steitz TA (2004) The structural mechanism of translocation and helicase activity in T7 RNA polymerase. Cell 116:393–404.PubMedCrossRefGoogle Scholar
  92. Ypma-Wong MF, Dewalt PG, Johnson VH, Lamb JG, Semler BL (1988) Protein 3CD is the major poliovirus proteinase responsible for cleavage of the P1 capsid precursor. Virology 166:265–270.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Kenneth K.-S. Ng
    • 1
  • Jamie J. Arnold
  • Craig E. Cameron
    • 2
  1. 1.Department of Biological SciencesUniversity of CalgaryCalgaryCanada
  2. 2.Department of Biochemistry and Molecular Biology The Pennsylvania State UniversityUniversity ParkUSA

Personalised recommendations