3kmq: Difference between revisions
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==G62S mutant of foot-and-mouth disease virus RNA-polymerase in complex with a template- primer RNA, tetragonal structure== | ==G62S mutant of foot-and-mouth disease virus RNA-polymerase in complex with a template- primer RNA, tetragonal structure== | ||
<StructureSection load='3kmq' size='340' side='right' caption='[[3kmq]], [[Resolution|resolution]] 2.11Å' scene=''> | <StructureSection load='3kmq' size='340' side='right'caption='[[3kmq]], [[Resolution|resolution]] 2.11Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3kmq]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3kmq]] 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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KMQ FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11Å</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=3kmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmq OCA], [https://pdbe.org/3kmq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kmq RCSB], [https://www.ebi.ac.uk/pdbsum/3kmq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kmq ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9QCE3_9PICO Q9QCE3_9PICO] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/3kmq_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/3kmq_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 30: | Line 30: | ||
==See Also== | ==See Also== | ||
*[[RNA polymerase|RNA polymerase]] | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Foot and mouth disease virus C]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Ferrer-Orta | [[Category: Ferrer-Orta C]] | ||
[[Category: Perez-Luque | [[Category: Perez-Luque R]] | ||
[[Category: Verdaguer | [[Category: Verdaguer N]] | ||
Latest revision as of 19:14, 1 November 2023
G62S mutant of foot-and-mouth disease virus RNA-polymerase in complex with a template- primer RNA, tetragonal structureG62S mutant of foot-and-mouth disease virus RNA-polymerase in complex with a template- primer RNA, tetragonal structure
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPassage of poliovirus (PV) or foot-and-mouth disease virus (FMDV) in the presence of ribavirin selected for viruses with decreased sensitivity to R, which included different mutations in their polymerase (3D): G64S located in the finger subdomain in the case of PV and M296I located within loop beta9-alpha11 at the active site in the case of FMDV. To investigate why disparate substitutions were selected in two closely related 3Ds, we constructed FMDVs with a 3D that included either G62S (the equivalent replacement in FMDV of PV G64S), M296I, or both substitutions. G62S, but not M296I, inflicts upon FMDV a strong selective disadvantage which is partially compensated for by the substitution M296I. The corresponding mutant polymerases, 3D(G62S), 3D(M296I), and 3D(G62S-M296I), were analyzed functionally and structurally. G62S in 3D impairs RNA-binding, polymerization, and R monophosphate incorporation activities. The X-ray structures of the 3D(G62S)-RNA, 3D(M296I)-RNA, and 3D(G62S-M296I)-RNA complexes show that although the two positions are separated by 13.1 A, the loops where the replacements reside are tightly connected through an extensive network of interactions that reach the polymerase active site. In particular, G62S seems to restrict the flexibility of loop beta9-alpha11 and, as a consequence, the flexibility of the active site and its ability to bind the RNA template. Thus, a localized change in the finger subdomain of 3D may affect the catalytic domain. The results provide a structural interpretation of why different amino acid substitutions were selected to confer R resistance in closely related viruses and reveal a complex network of intra-3D interactions that can affect the recognition of both the RNA template and incoming nucleotide. 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, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N J Virol. 2010 Jun;84(12):6188-99. Epub 2010 Apr 14. PMID:20392853[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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