1r6a
From Proteopedia
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- | [[Image:1r6a.png|left|200px]] | ||
- | + | ==Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate== | |
- | + | <StructureSection load='1r6a' size='340' side='right'caption='[[1r6a]], [[Resolution|resolution]] 2.60Å' scene=''> | |
- | + | == Structural highlights == | |
- | + | <table><tr><td colspan='2'>[[1r6a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_2_Puerto_Rico/PR159-S1/1969 Dengue virus 2 Puerto Rico/PR159-S1/1969]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R6A 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]] 2.6Å</td></tr> | |
- | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RVP:RIBAVIRIN+MONOPHOSPHATE'>RVP</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1r6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6a OCA], [https://pdbe.org/1r6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r6a RCSB], [https://www.ebi.ac.uk/pdbsum/1r6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r6a ProSAT]</span></td></tr> |
- | [[1r6a]] is a 1 chain structure with sequence from [ | + | </table> |
- | + | == Function == | |
- | == | + | [https://www.uniprot.org/uniprot/POLG_DEN2P POLG_DEN2P] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity). prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity). Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity). Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome (By similarity). Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential). Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity). Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity). Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity). Non-structural protein 4B inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity). |
- | < | + | == 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/r6/1r6a_consurf.spt"</scriptWhenChecked> |
- | [[Category: | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
- | [[Category: | + | <text>to colour the structure by Evolutionary Conservation</text> |
- | [[Category: | + | </jmolCheckbox> |
- | [[Category: | + | </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=1r6a ConSurf]. |
- | [[Category: | + | <div style="clear:both"></div> |
- | [[Category: | + | __TOC__ |
- | [[Category: | + | </StructureSection> |
+ | [[Category: Dengue virus 2 Puerto Rico/PR159-S1/1969]] | ||
+ | [[Category: Large Structures]] | ||
+ | [[Category: Benarroch D]] | ||
+ | [[Category: Canard B]] | ||
+ | [[Category: Egloff MP]] | ||
+ | [[Category: Mulard L]] | ||
+ | [[Category: Romette JL]] |
Current revision
Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate
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