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Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase.

Thompson AA, Peersen OB
EMBO J 23 3462-71 (2004)
Related entries: 1ra7, 1raj, 1tql

Cited: 177 times
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Abstract

The active RNA-dependent RNA polymerase of poliovirus, 3Dpol, is generated by cleavage of the 3CDpro precursor protein, a protease that has no polymerase activity despite containing the entire polymerase domain. By intentionally disrupting a known and persistent crystal packing interaction, we have crystallized the poliovirus polymerase in a new space group and solved the complete structure of the protein at 2.0 A resolution. It shows that the N-terminus of fully processed 3Dpol is buried in a surface pocket where it makes hydrogen bonds that act to position Asp238 in the active site. Asp238 is an essential residue that selects for the 2' OH group of substrate rNTPs, as shown by a 2.35 A structure of a 3Dpol-GTP complex. Mutational, biochemical, and structural data further demonstrate that 3Dpol activity is exquisitely sensitive to mutations at the N-terminus. This sensitivity is the result of allosteric effects where the structure around the buried N-terminus directly affects the positioning of Asp238 in the active site.

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  1. RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution. Venkataraman S, Prasad BVLS, Selvarajan R. Viruses 10 E76 (2018)
  2. A Structure-Function Diversity Survey of the RNA-Dependent RNA Polymerases From the Positive-Strand RNA Viruses. Jia H, Gong P. Front Microbiol 10 1945 (2019)
  3. RNA synthetic mechanisms employed by diverse families of RNA viruses. McDonald SM. Wiley Interdiscip Rev RNA 4 351-367 (2013)
  4. Picornaviral polymerase structure, function, and fidelity modulation. Peersen OB. Virus Res 234 4-20 (2017)
  5. Dynamics: the missing link between structure and function of the viral RNA-dependent RNA polymerase? Cameron CE, Moustafa IM, Arnold JJ. Curr Opin Struct Biol 19 768-774 (2009)
  6. RNA-Dependent RNA Polymerases of Picornaviruses: From the Structure to Regulatory Mechanisms. Ferrer-Orta C, Ferrero D, Verdaguer N. Viruses 7 4438-4460 (2015)
  7. Expanding knowledge of P3 proteins in the poliovirus lifecycle. Cameron CE, Oh HS, Moustafa IM. Future Microbiol 5 867-881 (2010)
  8. The uncoupling of catalysis and translocation in the viral RNA-dependent RNA polymerase. Shu B, Gong P. RNA Biol 14 1314-1319 (2017)
  9. Cystoviral RNA-directed RNA polymerases: Regulation of RNA synthesis on multiple time and length scales. Alphonse S, Ghose R. Virus Res 234 135-152 (2017)
  10. Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies. Ramaswamy K, Rashid M, Ramasamy S, Jayavelu T, Venkataraman S. Viruses 14 2200 (2022)

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  1. Structural basis for active site closure by the poliovirus RNA-dependent RNA polymerase. Gong P, Peersen OB. Proc Natl Acad Sci U S A 107 22505-22510 (2010)
  2. Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase. Thompson AA, Peersen OB. EMBO J 23 3462-3471 (2004)
  3. Nucleic acid polymerases use a general acid for nucleotidyl transfer. Castro C, Smidansky ED, Arnold JJ, Maksimchuk KR, Moustafa I, Uchida A, Götte M, Konigsberg W, Cameron CE. Nat Struct Mol Biol 16 212-218 (2009)
  4. Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase. Marcotte LL, Wass AB, Gohara DW, Pathak HB, Arnold JJ, Filman DJ, Cameron CE, Hogle JM. J Virol 81 3583-3596 (2007)
  5. Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity. Moustafa IM, Shen H, Morton B, Colina CM, Cameron CE. J Mol Biol 410 159-181 (2011)
  6. The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in complex with its protein primer VPg confirms the existence of a second VPg binding site on Picornaviridae polymerases. Gruez A, Selisko B, Roberts M, Bricogne G, Bussetta C, Jabafi I, Coutard B, De Palma AM, Neyts J, Canard B. J Virol 82 9577-9590 (2008)
  7. Structures of coxsackievirus, rhinovirus, and poliovirus polymerase elongation complexes solved by engineering RNA mediated crystal contacts. Gong P, Kortus MG, Nix JC, Davis RE, Peersen OB. PLoS One 8 e60272 (2013)
  8. Stabilization of poliovirus polymerase by NTP binding and fingers-thumb interactions. Thompson AA, Albertini RA, Peersen OB. J Mol Biol 366 1459-1474 (2007)
  9. Long-range interaction networks in the function and fidelity of poliovirus RNA-dependent RNA polymerase studied by nuclear magnetic resonance. Yang X, Welch JL, Arnold JJ, Boehr DD. Biochemistry 49 9361-9371 (2010)
  10. Distinct conformations of a putative translocation element in poliovirus polymerase. Sholders AJ, Peersen OB. J Mol Biol 426 1407-1419 (2014)
  11. Picornavirus genome replication. Identification of the surface of the poliovirus (PV) 3C dimer that interacts with PV 3Dpol during VPg uridylylation and construction of a structural model for the PV 3C2-3Dpol complex. Shen M, Reitman ZJ, Zhao Y, Moustafa I, Wang Q, Arnold JJ, Pathak HB, Cameron CE. J Biol Chem 283 875-888 (2008)
  12. Vaccine-derived mutation in motif D of poliovirus RNA-dependent RNA polymerase lowers nucleotide incorporation fidelity. Liu X, Yang X, Lee CA, Moustafa IM, Smidansky ED, Lum D, Arnold JJ, Cameron CE, Boehr DD. J Biol Chem 288 32753-32765 (2013)
  13. Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase. Freistadt MS, Vaccaro JA, Eberle KE. Virol J 4 44 (2007)
  14. What is the role of motif D in the nucleotide incorporation catalyzed by the RNA-dependent RNA polymerase from poliovirus? Shen H, Sun H, Li G. PLoS Comput Biol 8 e1002851 (2012)
  15. NMR structure of the viral peptide linked to the genome (VPg) of poliovirus. Schein CH, Oezguen N, Volk DE, Garimella R, Paul A, Braun W. Peptides 27 1676-1684 (2006)
  16. Highly similar structural frames link the template tunnel and NTP entry tunnel to the exterior surface in RNA-dependent RNA polymerases. Lang DM, Zemla AT, Zhou CL. Nucleic Acids Res 41 1464-1482 (2013)
  17. Structural dynamics as a contributor to error-prone replication by an RNA-dependent RNA polymerase. Moustafa IM, Korboukh VK, Arnold JJ, Smidansky ED, Marcotte LL, Gohara DW, Yang X, Sánchez-Farrán MA, Filman D, Maranas JK, Boehr DD, Hogle JM, Colina CM, Cameron CE. J Biol Chem 289 36229-36248 (2014)
  18. The crystal structure of a cardiovirus RNA-dependent RNA polymerase reveals an unusual conformation of the polymerase active site. Vives-Adrian L, Lujan C, Oliva B, van der Linden L, Selisko B, Coutard B, Canard B, van Kuppeveld FJ, Ferrer-Orta C, Verdaguer N. J Virol 88 5595-5607 (2014)
  19. Identification of tolerated insertion sites in poliovirus non-structural proteins. Teterina NL, Lauber C, Jensen KS, Levenson EA, Gorbalenya AE, Ehrenfeld E. Virology 409 1-11 (2011)
  20. A nucleobase-binding pocket in a viral RNA-dependent RNA polymerase contributes to elongation complex stability. Shi W, Ye HQ, Deng CL, Li R, Zhang B, Gong P. Nucleic Acids Res 48 1392-1405 (2020)
  21. Genome-wide networks of amino acid covariances are common among viruses. Donlin MJ, Szeto B, Gohara DW, Aurora R, Tavis JE. J Virol 86 3050-3063 (2012)
  22. NMR solution structure of poliovirus uridylyated peptide linked to the genome (VPgpU). Schein CH, Oezguen N, van der Heden van Noort GJ, Filippov DV, Paul A, Kumar E, Braun W. Peptides 31 1441-1448 (2010)
  23. StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase. Zemla AT, Lang DM, Kostova T, Andino R, Ecale Zhou CL. BMC Bioinformatics 12 226 (2011)
  24. Triphosphate Reorientation of the Incoming Nucleotide as a Fidelity Checkpoint in Viral RNA-dependent RNA Polymerases. Yang X, Liu X, Musser DM, Moustafa IM, Arnold JJ, Cameron CE, Boehr DD. J Biol Chem 292 3810-3826 (2017)
  25. Exploring the dynamics of four RNA-dependent RNA polymerases by a coarse-grained model. Shen H, Moustafa IM, Cameron CE, Colina CM. J Phys Chem B 116 14515-14524 (2012)
  26. Surface for catalysis by poliovirus RNA-dependent RNA polymerase. Wang J, Lyle JM, Bullitt E. J Mol Biol 425 2529-2540 (2013)
  27. Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome? Moustafa IM, Gohara DW, Uchida A, Yennawar N, Cameron CE. Viruses 7 5962-5986 (2015)
  28. Rational Control of Poliovirus RNA-Dependent RNA Polymerase Fidelity by Modulating Motif-D Loop Conformational Dynamics. Shi J, Perryman JM, Yang X, Liu X, Musser DM, Boehr AK, Moustafa IM, Arnold JJ, Cameron CE, Boehr DD. Biochemistry 58 3735-3743 (2019)
  29. Crystal Structure and Thermostability Characterization of Enterovirus D68 3Dpol. Wang C, Wang C, Li Q, Wang Z, Xie W. J Virol 91 e00876-17 (2017)
  30. Affinity labeling of hepatitis C virus replicase with a nucleotide analogue: identification of binding site. Manvar D, Singh K, Pandey VN. Biochemistry 52 432-444 (2013)
  31. Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase. Liu X, Musser DM, Lee CA, Yang X, Arnold JJ, Cameron CE, Boehr DD. Viruses 7 5571-5586 (2015)
  32. The Picornavirus Precursor 3CD Has Different Conformational Dynamics Compared to 3Cpro and 3Dpol in Functionally Relevant Regions. Winston DS, Boehr DD. Viruses 13 442 (2021)
  33. Crystal structure of a tick-borne flavivirus RNA-dependent RNA polymerase suggests a host adaptation hotspot in RNA viruses. Yang J, Jing X, Yi W, Li XD, Yao C, Zhang B, Zheng Z, Wang H, Gong P. Nucleic Acids Res 49 1567-1580 (2021)
  34. Induced intra- and intermolecular template switching as a therapeutic mechanism against RNA viruses. Janissen R, Woodman A, Shengjuler D, Vallet T, Lee KM, Kuijpers L, Moustafa IM, Fitzgerald F, Huang PN, Perkins AL, Harki DA, Arnold JJ, Solano B, Shih SR, Vignuzzi M, Cameron CE, Dekker NH. Mol Cell 81 4467-4480.e7 (2021)
  35. Tyr82 Amino Acid Mutation in PB1 Polymerase Induces an Influenza Virus Mutator Phenotype. Naito T, Shirai K, Mori K, Muratsu H, Ushirogawa H, Ohniwa RL, Hanada K, Saito M. J Virol 93 e00834-19 (2019)
  36. Novel viruses of the family Partitiviridae discovered in Saccharomyces cerevisiae. Taggart NT, Crabtree AM, Creagh JW, Bizarria R, Li S, de la Higuera I, Barnes JE, Shipley MA, Boyer JM, Stedman KM, Ytreberg FM, Rowley PA. PLoS Pathog 19 e1011418 (2023)
  37. Unusual substructure conformations observed in crystal structures of a dicistrovirus RNA-dependent RNA polymerase suggest contribution of the N-terminal extension in proper folding. Fang X, Lu G, Deng Y, Yang S, Hou C, Gong P. Virol Sin 38 531-540 (2023)


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  2. Structure-function relationships among RNA-dependent RNA polymerases. Ng KK, Arnold JJ, Cameron CE. Curr Top Microbiol Immunol 320 137-156 (2008)
  3. Common and unique features of viral RNA-dependent polymerases. te Velthuis AJ. Cell Mol Life Sci 71 4403-4420 (2014)
  4. Cis-active RNA elements (CREs) and picornavirus RNA replication. Steil BP, Barton DJ. Virus Res 139 240-252 (2009)
  5. Nucleosides for the treatment of respiratory RNA virus infections. Jordan PC, Stevens SK, Deval J. Antivir Chem Chemother 26 2040206618764483 (2018)
  6. Nidovirus RNA polymerases: Complex enzymes handling exceptional RNA genomes. Posthuma CC, Te Velthuis AJW, Snijder EJ. Virus Res 234 58-73 (2017)
  7. A Structural Overview of RNA-Dependent RNA Polymerases from the Flaviviridae Family. Wu J, Liu W, Gong P. Int J Mol Sci 16 12943-12957 (2015)
  8. RNA-dependent RNA polymerases from Flaviviridae. Choi KH, Rossmann MG. Curr Opin Struct Biol 19 746-751 (2009)
  9. Viral polymerases. Choi KH. Adv Exp Med Biol 726 267-304 (2012)
  10. Fidelity Variants and RNA Quasispecies. Bordería AV, Rozen-Gagnon K, Vignuzzi M. Curr Top Microbiol Immunol 392 303-322 (2016)
  11. Structure and function of RNA replication. Ortín J, Parra F. Annu Rev Microbiol 60 305-326 (2006)
  12. Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge. Picarazzi F, Vicenti I, Saladini F, Zazzi M, Mori M. Molecules 25 E5695 (2020)
  13. RNA-dependent RNA polymerases from flaviviruses and Picornaviridae. Lescar J, Canard B. Curr Opin Struct Biol 19 759-767 (2009)
  14. A structural view of the RNA-dependent RNA polymerases from the Flavivirus genus. Lu G, Gong P. Virus Res 234 34-43 (2017)
  15. Practical application of bioinformatics by the multidisciplinary VIZIER consortium. Gorbalenya AE, Lieutaud P, Harris MR, Coutard B, Canard B, Kleywegt GJ, Kravchenko AA, Samborskiy DV, Sidorov IA, Leontovich AM, Jones TA. Antiviral Res 87 95-110 (2010)
  16. Innate host barriers to viral trafficking and population diversity: lessons learned from poliovirus. Pfeiffer JK. Adv Virus Res 77 85-118 (2010)
  17. Picornavirus RNA-dependent RNA polymerase. Kok CC, McMinn PC. Int J Biochem Cell Biol 41 498-502 (2009)
  18. Three-dimensional structure of foot-and-mouth disease virus and its biological functions. Han SC, Guo HC, Sun SQ. Arch Virol 160 1-16 (2015)
  19. A 21st century perspective of poliovirus replication. Lévêque N, Semler BL. PLoS Pathog 11 e1004825 (2015)
  20. Fidelity of Nucleotide Incorporation by the RNA-Dependent RNA Polymerase from Poliovirus. Cameron CE, Moustafa IM, Arnold JJ. Enzymes 39 293-323 (2016)
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  22. Structural organization of viral RNA-dependent RNA polymerases. Shatskaya GS, Dmitrieva TM. Biochemistry (Mosc) 78 231-235 (2013)
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  1. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R. Nature 439 344-348 (2006)
  2. Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution. Yap TL, Xu T, Chen YL, Malet H, Egloff MP, Canard B, Vasudevan SG, Lescar J. J Virol 81 4753-4765 (2007)
  3. Engineering attenuated virus vaccines by controlling replication fidelity. Vignuzzi M, Wendt E, Andino R. Nat Med 14 154-161 (2008)
  4. A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, Ferron F, Gorbalenya AE, Canard B. EMBO J 25 4933-4942 (2006)
  5. Arbovirus high fidelity variant loses fitness in mosquitoes and mice. Coffey LL, Beeharry Y, Bordería AV, Blanc H, Vignuzzi M. Proc Natl Acad Sci U S A 108 16038-16043 (2011)
  6. The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent. te Velthuis AJ, Arnold JJ, Cameron CE, van den Worm SH, Snijder EJ. Nucleic Acids Res 38 203-214 (2010)
  7. Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. Lu G, Gong P. PLoS Pathog 9 e1003549 (2013)
  8. The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. te Velthuis AJ, van den Worm SH, Snijder EJ. Nucleic Acids Res 40 1737-1747 (2012)
  9. Remote site control of an active site fidelity checkpoint in a viral RNA-dependent RNA polymerase. Arnold JJ, Vignuzzi M, Stone JK, Andino R, Cameron CE. J Biol Chem 280 25706-25716 (2005)
  10. Foot-and-mouth disease virus mutant with decreased sensitivity to ribavirin: implications for error catastrophe. Sierra M, Airaksinen A, González-López C, Agudo R, Arias A, Domingo E. J Virol 81 2012-2024 (2007)
  11. Coxsackievirus B3 mutator strains are attenuated in vivo. Gnädig NF, Beaucourt S, Campagnola G, Bordería AV, Sanz-Ramos M, Gong P, Blanc H, Peersen OB, Vignuzzi M. Proc Natl Acad Sci U S A 109 E2294-303 (2012)
  12. The structure of a protein primer-polymerase complex in the initiation of genome replication. Ferrer-Orta C, Arias A, Agudo R, Pérez-Luque R, Escarmís C, Domingo E, Verdaguer N. EMBO J 25 880-888 (2006)
  13. Determinants of RNA-dependent RNA polymerase (in)fidelity revealed by kinetic analysis of the polymerase encoded by a foot-and-mouth disease virus mutant with reduced sensitivity to ribavirin. Arias A, Arnold JJ, Sierra M, Smidansky ED, Domingo E, Cameron CE. J Virol 82 12346-12355 (2008)
  14. Structural basis of viral RNA-dependent RNA polymerase catalysis and translocation. Shu B, Gong P. Proc Natl Acad Sci U S A 113 E4005-14 (2016)
  15. Poliovirus proteins induce membrane association of GTPase ADP-ribosylation factor. Belov GA, Fogg MH, Ehrenfeld E. J Virol 79 7207-7216 (2005)
  16. Petabase-scale sequence alignment catalyses viral discovery. Edgar RC, Taylor J, Lin V, Altman T, Barbera P, Meleshko D, Lohr D, Novakovsky G, Buchfink B, Al-Shayeb B, Banfield JF, de la Peña M, Korobeynikov A, Chikhi R, Babaian A. Nature 602 142-147 (2022)
  17. Structure-function relationships underlying the replication fidelity of viral RNA-dependent RNA polymerases. Campagnola G, McDonald S, Beaucourt S, Vignuzzi M, Peersen OB. J Virol 89 275-286 (2015)
  18. Analysis of flavivirus NS5 methyltransferase cap binding. Geiss BJ, Thompson AA, Andrews AJ, Sons RL, Gari HH, Keenan SM, Peersen OB. J Mol Biol 385 1643-1654 (2009)
  19. Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds. Levi LI, Gnädig NF, Beaucourt S, McPherson MJ, Baron B, Arnold JJ, Vignuzzi M. PLoS Pathog 6 e1001163 (2010)
  20. Activation mechanism of a noncanonical RNA-dependent RNA polymerase. Garriga D, Navarro A, Querol-Audí J, Abaitua F, Rodríguez JF, Verdaguer N. Proc Natl Acad Sci U S A 104 20540-20545 (2007)
  21. Attenuation of human enterovirus 71 high-replication-fidelity variants in AG129 mice. Meng T, Kwang J. J Virol 88 5803-5815 (2014)
  22. Structural and functional characterization of sapovirus RNA-dependent RNA polymerase. Fullerton SW, Blaschke M, Coutard B, Gebhardt J, Gorbalenya A, Canard B, Tucker PA, Rohayem J. J Virol 81 1858-1871 (2007)
  23. Factors required for the Uridylylation of the foot-and-mouth disease virus 3B1, 3B2, and 3B3 peptides by the RNA-dependent RNA polymerase (3Dpol) in vitro. Nayak A, Goodfellow IG, Belsham GJ. J Virol 79 7698-7706 (2005)
  24. De novo initiation of RNA synthesis by the arterivirus RNA-dependent RNA polymerase. Beerens N, Selisko B, Ricagno S, Imbert I, van der Zanden L, Snijder EJ, Canard B. J Virol 81 8384-8395 (2007)
  25. Activation of cellular Arf GTPases by poliovirus protein 3CD correlates with virus replication. Belov GA, Habbersett C, Franco D, Ehrenfeld E. J Virol 81 9259-9267 (2007)
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  27. The role of the priming loop in influenza A virus RNA synthesis. Te Velthuis AJ, Robb NC, Kapanidis AN, Fodor E. Nat Microbiol 1 16029 (2016)
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  29. Novel antiviral agent DTriP-22 targets RNA-dependent RNA polymerase of enterovirus 71. Chen TC, Chang HY, Lin PF, Chern JH, Hsu JT, Chang CY, Shih SR. Antimicrob Agents Chemother 53 2740-2747 (2009)
  30. Structure of foot-and-mouth disease virus mutant polymerases with reduced sensitivity to ribavirin. Ferrer-Orta C, Sierra M, Agudo R, de la Higuera I, Arias A, Pérez-Luque R, Escarmís C, Domingo E, Verdaguer N. J Virol 84 6188-6199 (2010)
  31. Structure-function relationships of the viral RNA-dependent RNA polymerase: fidelity, replication speed, and initiation mechanism determined by a residue in the ribose-binding pocket. Korneeva VS, Cameron CE. J Biol Chem 282 16135-16145 (2007)
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  33. Ribavirin-resistant mutants of human enterovirus 71 express a high replication fidelity phenotype during growth in cell culture. Sadeghipour S, Bek EJ, McMinn PC. J Virol 87 1759-1769 (2013)
  34. Binding of 2'-amino-2'-deoxycytidine-5'-triphosphate to norovirus polymerase induces rearrangement of the active site. Zamyatkin DF, Parra F, Machín A, Grochulski P, Ng KK. J Mol Biol 390 10-16 (2009)
  35. The active form of the norovirus RNA-dependent RNA polymerase is a homodimer with cooperative activity. Högbom M, Jäger K, Robel I, Unge T, Rohayem J. J Gen Virol 90 281-291 (2009)
  36. Crystal structure of coxsackievirus B3 3Dpol highlights the functional importance of residue 5 in picornavirus polymerases. Campagnola G, Weygandt M, Scoggin K, Peersen O. J Virol 82 9458-9464 (2008)
  37. Picornavirus genome replication: roles of precursor proteins and rate-limiting steps in oriI-dependent VPg uridylylation. Pathak HB, Oh HS, Goodfellow IG, Arnold JJ, Cameron CE. J Biol Chem 283 30677-30688 (2008)
  38. Comparative genomic analysis of coxsackievirus A6 strains of different clinical disease entities. Chen YJ, Chang SC, Tsao KC, Shih SR, Yang SL, Lin TY, Huang YC. PLoS One 7 e52432 (2012)
  39. Mutant viral polymerase in the transition of virus to error catastrophe identifies a critical site for RNA binding. Arias A, Agudo R, Ferrer-Orta C, Pérez-Luque R, Airaksinen A, Brocchi E, Domingo E, Verdaguer N, Escarmís C. J Mol Biol 353 1021-1032 (2005)
  40. Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8. Liu YC, Kuo RL, Lin JY, Huang PN, Huang Y, Liu H, Arnold JJ, Chen SJ, Wang RY, Cameron CE, Shih SR. PLoS Pathog 10 e1004199 (2014)
  41. Enzymatic and nonenzymatic functions of viral RNA-dependent RNA polymerases within oligomeric arrays. Spagnolo JF, Rossignol E, Bullitt E, Kirkegaard K. RNA 16 382-393 (2010)
  42. Inhibition of enterovirus 71 by adenosine analog NITD008. Deng CL, Yeo H, Ye HQ, Liu SQ, Shang BD, Gong P, Alonso S, Shi PY, Zhang B. J Virol 88 11915-11923 (2014)
  43. Amiloride derivatives inhibit coxsackievirus B3 RNA replication. Harrison DN, Gazina EV, Purcell DF, Anderson DA, Anderson DA, Petrou S. J Virol 82 1465-1473 (2008)
  44. The RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family. van der Linden L, Vives-Adrián L, Selisko B, Ferrer-Orta C, Liu X, Lanke K, Ulferts R, De Palma AM, Tanchis F, Goris N, Lefebvre D, De Clercq K, Leyssen P, Lacroix C, Pürstinger G, Coutard B, Canard B, Boehr DD, Arnold JJ, Cameron CE, Verdaguer N, Neyts J, van Kuppeveld FJ. PLoS Pathog 11 e1004733 (2015)
  45. Genome sequence and molecular characterization of Homalodisca coagulata virus-1, a novel virus discovered in the glassy-winged sharpshooter (Hemiptera: Cicadellidae). Hunnicutt LE, Hunter WB, Cave RD, Powell CA, Mozoruk JJ. Virology 350 67-78 (2006)
  46. Perturbation in the conserved methyltransferase-polymerase interface of flavivirus NS5 differentially affects polymerase initiation and elongation. Wu J, Lu G, Zhang B, Gong P. J Virol 89 249-261 (2015)
  47. A template RNA entry channel in the fingers domain of the poliovirus polymerase. Kortus MG, Kempf BJ, Haworth KG, Barton DJ, Peersen OB. J Mol Biol 417 263-278 (2012)
  48. Proteolytic processing of turnip yellow mosaic virus replication proteins and functional impact on infectivity. Jakubiec A, Drugeon G, Camborde L, Jupin I. J Virol 81 11402-11412 (2007)
  49. RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator nucleotide GTP to form a mechanistically important pre-initiation state. Surana P, Satchidanandam V, Nair DT. Nucleic Acids Res 42 2758-2773 (2014)
  50. A quantitative stopped-flow fluorescence assay for measuring polymerase elongation rates. Gong P, Campagnola G, Peersen OB. Anal Biochem 391 45-55 (2009)
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  52. Intramolecular and intermolecular uridylylation by poliovirus RNA-dependent RNA polymerase. Richards OC, Spagnolo JF, Lyle JM, Vleck SE, Kuchta RD, Kirkegaard K. J Virol 80 7405-7415 (2006)
  53. Small ubiquitin-like modifying protein isopeptidase assay based on poliovirus RNA polymerase activity. Arnold JJ, Bernal A, Uche U, Sterner DE, Butt TR, Cameron CE, Mattern MR. Anal Biochem 350 214-221 (2006)
  54. In Vitro Assessment of Combinations of Enterovirus Inhibitors against Enterovirus 71. Wang Y, Li G, Yuan S, Gao Q, Lan K, Altmeyer R, Zou G. Antimicrob Agents Chemother 60 5357-5367 (2016)
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  56. Allosteric effects of ligands and mutations on poliovirus RNA-dependent RNA polymerase. Boerner JE, Lyle JM, Daijogo S, Semler BL, Schultz SC, Kirkegaard K, Richards OC. J Virol 79 7803-7811 (2005)
  57. Nucleotide channel of RNA-dependent RNA polymerase used for intermolecular uridylylation of protein primer. Tellez AB, Crowder S, Spagnolo JF, Thompson AA, Peersen OB, Brutlag DL, Kirkegaard K. J Mol Biol 357 665-675 (2006)
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  59. The Structure of the RNA-Dependent RNA Polymerase of a Permutotetravirus Suggests a Link between Primer-Dependent and Primer-Independent Polymerases. Ferrero DS, Buxaderas M, Rodríguez JF, Verdaguer N. PLoS Pathog 11 e1005265 (2015)
  60. A Cell-Based Reporter Assay for Screening Inhibitors of MERS Coronavirus RNA-Dependent RNA Polymerase Activity. Min JS, Kim GW, Kwon S, Jin YH. J Clin Med 9 E2399 (2020)
  61. Stimulation of poliovirus RNA synthesis and virus maturation in a HeLa cell-free in vitro translation-RNA replication system by viral protein 3CDpro. Franco D, Pathak HB, Cameron CE, Rombaut B, Wimmer E, Paul AV. Virol J 2 86 (2005)
  62. Selection and characterization of RNA aptamers to the RNA-dependent RNA polymerase from foot-and-mouth disease virus. Ellingham M, Bunka DH, Rowlands DJ, Stonehouse NJ. RNA 12 1970-1979 (2006)
  63. Viral precursor protein P3 and its processed products perform discrete and essential functions in the poliovirus RNA replication complex. Spear A, Ogram SA, Morasco BJ, Smerage LE, Flanegan JB. Virology 485 492-501 (2015)
  64. A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase. Wu J, Ye HQ, Zhang QY, Lu G, Zhang B, Gong P. PLoS Pathog 16 e1008484 (2020)
  65. Characterization of protein-protein interactions critical for poliovirus replication: analysis of 3AB and VPg binding to the RNA-dependent RNA polymerase. Strauss DM, Wuttke DS. J Virol 81 6369-6378 (2007)
  66. Structural features of a picornavirus polymerase involved in the polyadenylation of viral RNA. Kempf BJ, Kelly MM, Springer CL, Peersen OB, Barton DJ. J Virol 87 5629-5644 (2013)
  67. A unique intra-molecular fidelity-modulating mechanism identified in a viral RNA-dependent RNA polymerase. Liu W, Shi X, Gong P. Nucleic Acids Res 46 10840-10854 (2018)
  68. Interstitial contacts in an RNA-dependent RNA polymerase lattice. Tellez AB, Wang J, Tanner EJ, Spagnolo JF, Kirkegaard K, Bullitt E. J Mol Biol 412 737-750 (2011)
  69. Structural models for the design of novel antiviral agents against Greek Goat Encephalitis. Papageorgiou L, Loukatou S, Koumandou VL, Makałowski W, Megalooikonomou V, Vlachakis D, Kossida S. PeerJ 2 e664 (2014)
  70. Comparison of poliovirus recombinants: accumulation of point mutations provides further advantages. Savolainen-Kopra C, Samoilovich E, Kahelin H, Hiekka AK, Hovi T, Roivainen M. J Gen Virol 90 1859-1868 (2009)
  71. Novel, structure-based mechanism for uridylylation of the genome-linked peptide (VPg) of picornaviruses. Schein CH, Volk DE, Oezguen N, Paul A. Proteins 63 719-726 (2006)
  72. Prediction of Small Molecule Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus-2 RNA-dependent RNA Polymerase. Ahmad M, Dwivedy A, Mariadasse R, Tiwari S, Kar D, Jeyakanthan J, Biswal BK. ACS Omega 5 18356-18366 (2020)
  73. The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide-Binding Domain. Shengjuler D, Chan YM, Sun S, Moustafa IM, Li ZL, Gohara DW, Buck M, Cremer PS, Boehr DD, Cameron CE. Structure 25 1875-1886.e7 (2017)
  74. BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71. Velu AB, Chen GW, Hsieh PT, Horng JT, Hsu JT, Hsieh HP, Chen TC, Weng KF, Shih SR. Antiviral Res 112 18-25 (2014)
  75. Significance of the C-terminal amino acid residue in mengovirus RNA-dependent RNA polymerase. Dmitrieva TM, Alexeevski AV, Shatskaya GS, Tolskaya EA, Gmyl AP, Khitrina EV, Agol VI. Virology 365 79-91 (2007)
  76. UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication. Huang PN, Jheng JR, Arnold JJ, Wang JR, Cameron CE, Shih SR. PLoS Pathog 13 e1006375 (2017)
  77. Non-DNA-templated addition of nucleotides to the 3' end of RNAs by the mitochondrial RNA polymerase of Physarum polycephalum. Miller ML, Miller DL. Mol Cell Biol 28 5795-5802 (2008)
  78. Polyprotein context regulates the activity of poliovirus 2CATPase bound to bilayer nanodiscs. Springer CL, Huntoon HP, Peersen OB. J Virol 87 5994-6004 (2013)
  79. Determinants in 3Dpol modulate the rate of growth of hepatitis A virus. Konduru K, Kaplan GG. J Virol 84 8342-8347 (2010)
  80. Functional characterization of fingers subdomain-specific monoclonal antibodies inhibiting the hepatitis C virus RNA-dependent RNA polymerase. Nikonov A, Juronen E, Ustav M. J Biol Chem 283 24089-24102 (2008)
  81. Peptide Synthesis on a Next-Generation DNA Sequencing Platform. Svensen N, Peersen OB, Jaffrey SR. Chembiochem 17 1628-1635 (2016)
  82. SARS-CoV-2 RdRp Inhibitors Selected from a Cell-Based SARS-CoV-2 RdRp Activity Assay System. Min JS, Kwon S, Jin YH. Biomedicines 9 996 (2021)
  83. Dominant CD4-dependent RNA-dependent RNA polymerase-specific T-cell responses in children acutely infected with human enterovirus 71 and healthy adult controls. Dang S, Gao N, Li Y, Li M, Wang X, Jia X, Zhai S, Zhang X, Liu J, Deng H, Dong T. Immunology 142 89-100 (2014)
  84. Homology modeling and analysis of structure predictions of the bovine rhinitis B virus RNA dependent RNA polymerase (RdRp). Rai DK, Rieder E. Int J Mol Sci 13 8998-9013 (2012)
  85. Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs. Maheden K, Todd B, Gordon CJ, Tchesnokov EP, Götte M. Enzymes 49 315-354 (2021)
  86. Independent evolution of tetraloop in enterovirus oriL replicative element and its putative binding partners in virus protein 3C. Prostova MA, Deviatkin AA, Tcelykh IO, Lukashev AN, Gmyl AP. PeerJ 5 e3896 (2017)
  87. The RNA-dependent RNA polymerase of Citrus tristeza virus forms oligomers. Cevik B. Virology 447 121-130 (2013)
  88. The role of the priming loop in Influenza A virus RNA synthesis. Te Velthuis AJ, Robb NC, Kapanidis AN, Fodor E. Nat Microbiol 1 16029 (2016)
  89. An all-atom, active site exploration of antiviral drugs that target Flaviviridae polymerases. Valdés JJ, Gil VA, Butterill PT, Růžek D. J Gen Virol 97 2552-2565 (2016)
  90. Improved crystallization of the coxsackievirus B3 RNA-dependent RNA polymerase. Jabafi I, Selisko B, Coutard B, De Palma AM, Neyts J, Egloff MP, Grisel S, Dalle K, Campanacci V, Spinelli S, Cambillau C, Canard B, Gruez A. Acta Crystallogr Sect F Struct Biol Cryst Commun 63 495-498 (2007)
  91. Investigation of activity of recombinant mengovirus RNA-dependent RNA polymerase and its mutants. Shatskaya GS, Drutsa VL, Koroleva ON, Osterman IA, Dmitrieva TM. Biochemistry (Mosc) 78 96-101 (2013)
  92. Molecular characterization of a novel cryptic virus infecting pigeonpea plants. Kumar S, Subbarao BL, Kumari R, Hallan V. PLoS One 12 e0181829 (2017)
  93. Amiloride inhibits the initiation of Coxsackievirus and poliovirus RNA replication by inhibiting VPg uridylylation. Ogram SA, Boone CD, McKenna R, Flanegan JB. Virology 464-465 87-97 (2014)
  94. An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase. Zhang BY, Liu W, Jia H, Lu G, Gong P. Nucleic Acids Res 49 8811-8821 (2021)
  95. The SARS-CoV nsp12 Polymerase Active Site Is Tuned for Large-Genome Replication. Campagnola G, Govindarajan V, Pelletier A, Canard B, Peersen OB. J Virol 96 e0067122 (2022)
  96. Within and Beyond the Nucleotide Addition Cycle of Viral RNA-dependent RNA Polymerases. Gong P. Front Mol Biosci 8 822218 (2021)
  97. A comparative analysis of parechovirus protein structures with other picornaviruses. Domanska A, Guryanov S, Butcher SJ. Open Biol 11 210008 (2021)
  98. An Extended Primer Grip of Picornavirus Polymerase Facilitates Sexual RNA Replication Mechanisms. Kempf BJ, Watkins CL, Peersen OB, Barton DJ. J Virol 94 e00835-20 (2020)
  99. Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons. Freistadt MS, Eberle KE. Virol J 4 28 (2007)
  100. ERDRP-0519 inhibits feline coronavirus in vitro. Camero M, Lanave G, Catella C, Lucente MS, Sposato A, Mari V, Tempesta M, Martella V, Buonavoglia A. BMC Vet Res 18 55 (2022)
  101. Globular domain structure and function of restriction-like-endonuclease LINEs: similarities to eukaryotic splicing factor Prp8. Mahbub MM, Chowdhury SM, Christensen SM. Mob DNA 8 16 (2017)
  102. Novel roles of the picornaviral 3D polymerase in viral pathogenesis. Kerkvliet J, Edukulla R, Rodriguez M. Adv Virol 2010 368068 (2010)
  103. Picornaviral polymerase domain exchanges reveal a modular basis for distinct biochemical activities of viral RNA-dependent RNA polymerases. Watkins CL, Kempf BJ, Beaucourt S, Barton DJ, Peersen OB. J Biol Chem 295 10624-10637 (2020)
  104. Co-folding and RNA activation of poliovirus 3Cpro polyprotein precursors. Campagnola G, Peersen O. J Biol Chem 299 105258 (2023)
  105. Dual role of the foot-and-mouth disease virus 3B1 protein in the replication complex: As protein primer and as an essential component to recruit 3Dpol to membranes. Ferrer-Orta C, Ferrero DS, Verdaguer N. PLoS Pathog 19 e1011373 (2023)
  106. Favipiravir Does Not Inhibit Chikungunya Virus Replication in Mosquito Cells and Aedes aegypti Mosquitoes. Jacobs S, Wang L, Rosales Rosas AL, Van Berwaer R, Vanderlinden E, Failloux AB, Naesens L, Delang L. Microorganisms 9 944 (2021)
  107. Identification of Mulberrofuran as a potent inhibitor of hepatitis A virus 3Cpro and RdRP enzymes through structure-based virtual screening, dynamics simulation, and DFT studies. Sureshan M, Brintha S, Jothi A. Mol Divers (2023)


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