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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4iqx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot_and_mouth_disease_virus_C Foot and mouth disease virus C] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQX FirstGlance]. <br>
<table><tr><td colspan='2'>[[4iqx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot_and_mouth_disease_virus_C Foot and mouth disease virus C] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQX FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4iqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqx OCA], [https://pdbe.org/4iqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iqx RCSB], [https://www.ebi.ac.uk/pdbsum/4iqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqx ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4iqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqx OCA], [https://pdbe.org/4iqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iqx RCSB], [https://www.ebi.ac.uk/pdbsum/4iqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqx ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/Q9QCE4_9PICO Q9QCE4_9PICO] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266]  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047]
[https://www.uniprot.org/uniprot/Q9QCE4_9PICO Q9QCE4_9PICO] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266]  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047]
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== Publication Abstract from PubMed ==
Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-beta-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is mediated by amino acid substitutions in the viral polymerase that either increase the general template copying fidelity of the enzyme or decrease the incorporation of ribavirin into RNA. Here we describe experiments that show that replication of the important picornavirus pathogen foot-and-mouth disease virus (FMDV) in the presence of increasing concentrations of ribavirin results in the sequential incorporation of three amino acid substitutions (M296I, P44S and P169S) in the viral polymerase (3D). The main biological effect of these substitutions is to attenuate the consequences of the mutagenic activity of ribavirin -by avoiding the biased repertoire of transition mutations produced by this purine analogue-and to maintain the replicative fitness of the virus which is able to escape extinction by ribavirin. This is achieved through alteration of the pairing behavior of ribavirin-triphosphate (RTP), as evidenced by in vitro polymerization assays with purified mutant 3Ds. Comparison of the three-dimensional structure of wild type and mutant polymerases suggests that the amino acid substitutions alter the position of the template RNA in the entry channel of the enzyme, thereby affecting nucleotide recognition. The results provide evidence of a new mechanism of resistance to a mutagenic nucleoside analogue which allows the virus to maintain a balance among mutation types introduced into progeny genomes during replication under strong mutagenic pressure.
A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape.,Agudo R, Ferrer-Orta C, Arias A, de la Higuera I, Perales C, Perez-Luque R, Verdaguer N, Domingo E PLoS Pathog. 2010 Aug 26;6(8). pii: e1001072. PMID:20865120<ref>PMID:20865120</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4iqx" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
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