View source for 2e9r


==Foot-and-mouth disease virus RNA-dependent RNA polymerase in complex with a template-primer RNA and with ribavirin==
<StructureSection load='2e9r' size='340' side='right'caption='[[2e9r]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2e9r]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Foot-and-mouth_disease_virus_C-S8c1 Foot-and-mouth disease virus C-S8c1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2E9R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2E9R FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.81&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RTP:RIBAVIRIN+TRIPHOSPHATE'>RTP</scene></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=2e9r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e9r OCA], [https://pdbe.org/2e9r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2e9r RCSB], [https://www.ebi.ac.uk/pdbsum/2e9r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2e9r ProSAT]</span></td></tr>
</table>
== 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]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/2e9r_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2e9r ConSurf].
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== Publication Abstract from PubMed ==
RNA virus replication is an error-prone event caused by the low fidelity of viral RNA-dependent RNA polymerases. Replication fidelity can be decreased further by the use of mutagenic ribonucleoside analogs to a point where viral genetic information can no longer be maintained. For foot-and-mouth disease virus, the antiviral analogs ribavirin and 5-fluorouracil have been shown to be mutagenic, contributing to virus extinction through lethal mutagenesis. Here, we report the x-ray structure of four elongation complexes of foot-and-mouth disease virus polymerase 3D obtained in presence of natural substrates, ATP and UTP, or mutagenic nucleotides, ribavirin triphosphate and 5-fluorouridine triphosphate with different RNAs as template-primer molecules. The ability of these complexes to synthesize RNA in crystals allowed us to capture different successive replication events and to define the critical amino acids involved in (i) the recognition and positioning of the incoming nucleotide or analog; (ii) the positioning of the acceptor base of the template strand; and (iii) the positioning of the 3'-OH group of the primer nucleotide during RNA replication. The structures identify key interactions involved in viral RNA replication and provide insights into the molecular basis of the low fidelity of viral RNA polymerases.

Sequential structures provide insights into the fidelity of RNA replication.,Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N Proc Natl Acad Sci U S A. 2007 May 29;104(22):9463-8. Epub 2007 May 21. PMID:17517631<ref>PMID:17517631</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 2e9r" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Foot-and-mouth disease virus C-S8c1]]
[[Category: Large Structures]]
[[Category: Arias A]]
[[Category: Domingo E]]
[[Category: Escarmis C]]
[[Category: Ferrer-Orta C]]
[[Category: Perez-Luque R]]
[[Category: Verdaguer N]]