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| | ==Mutant P44S M296I of Foot-and-mouth disease Virus RNA-dependent RNA polymerase== | | ==Mutant P44S M296I of Foot-and-mouth disease Virus RNA-dependent RNA polymerase== |
| - | <StructureSection load='3nl0' size='340' side='right' caption='[[3nl0]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='3nl0' size='340' side='right'caption='[[3nl0]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nl0]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Foot-and-mouth_disease_virus_-_type_c Foot-and-mouth disease virus - type c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NL0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NL0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nl0]] 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=3NL0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NL0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wne|1wne]], [[1u09|1u09]], [[2e9r|2e9r]], [[2e9t|2e9t]], [[2e9z|2e9z]], [[2ec0|2ec0]], [[3nky|3nky]]</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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12116 Foot-and-mouth disease virus - type C])</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=3nl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nl0 OCA], [https://pdbe.org/3nl0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nl0 RCSB], [https://www.ebi.ac.uk/pdbsum/3nl0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nl0 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3nl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nl0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nl0 RCSB], [http://www.ebi.ac.uk/pdbsum/3nl0 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3nl0" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==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: Foot-and-mouth disease virus - type c]] | + | [[Category: Foot and mouth disease virus C]] |
| - | [[Category: Agudo, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Arias, A]] | + | [[Category: Agudo R]] |
| - | [[Category: Domingo, E]] | + | [[Category: Arias A]] |
| - | [[Category: Ferrer-Orta, C]] | + | [[Category: Domingo E]] |
| - | [[Category: Perez-Luque, R]] | + | [[Category: Ferrer-Orta C]] |
| - | [[Category: Verdaguer, N]] | + | [[Category: Perez-Luque R]] |
| - | [[Category: 3d polymerase]]
| + | [[Category: Verdaguer N]] |
| - | [[Category: Foot-and-mouth disease virus picornavirus]]
| + | |
| - | [[Category: Rna dependent rna polymerase]]
| + | |
| - | [[Category: Transferase-rna complex]]
| + | |
| Structural highlights
Function
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]
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Agudo R, Ferrer-Orta C, Arias A, de la Higuera I, Perales C, Perez-Luque R, Verdaguer N, Domingo E. A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape. PLoS Pathog. 2010 Aug 26;6(8). pii: e1001072. PMID:20865120 doi:10.1371/journal.ppat.1001072
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