View source for 5xc6


==Dengue Virus 4 NS3 Helicase in complex with SSRNA SLA12==
<StructureSection load='5xc6' size='340' side='right'caption='[[5xc6]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xc6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Dengue_virus_4 Dengue virus 4] 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=5XC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XC6 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5xc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xc6 OCA], [https://pdbe.org/5xc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xc6 RCSB], [https://www.ebi.ac.uk/pdbsum/5xc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xc6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/M9P7S0_9FLAV M9P7S0_9FLAV] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[SAAS:SAAS00882589]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The protein-RNA interactions within the flavivirus replication complex (RC) are not fully understood. Our structure of dengue virus NS3 adenosine triphosphatase (ATPase)/helicase bound to the conserved 5' genomic RNA 5'-AGUUGUUAGUCU-3' reveals that D290 and R538 make specific interactions with G2 and G5 bases respectively. We show that single-stranded 12-mer RNA stimulates ATPase activity of NS3, however the presence of G2 and G5 leads to significantly higher activation. D290 is adjacent to the DEXH motif found in SF2 helicases like NS3 and interacts with R387, forming a molecular switch that activates the ATPase site upon RNA binding. Our structure guided mutagenesis revealed that disruption of D290-R387 interaction increases basal ATPase activity presumably as a result of higher conformational flexibility of the ATPase active site. Mutational studies also showed R538 plays a critical role in RNA interactions affecting translocation of viral RNA through dynamic interactions with bases at positions 4 and 5 of the ssRNA. Restriction of backbone flexibility around R538 through mutation of G540 to proline abolishes virus replication, indicating conformational flexibility around residue R538 is necessary for RNA translocation. The functionally critical sequence-specific contacts in NS3 RNA binding groove in subdomain III reveals potentially novel allosteric anti-viral drug targets.

NS3 helicase from dengue virus specifically recognizes viral RNA sequence to ensure optimal replication.,Swarbrick CMD, Basavannacharya C, Chan KWK, Chan SA, Singh D, Wei N, Phoo WW, Luo D, Lescar J, Vasudevan SG Nucleic Acids Res. 2017 Nov 20. pii: 4641900. doi: 10.1093/nar/gkx1127. PMID:29165589<ref>PMID:29165589</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xc6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Helicase 3D structures|Helicase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dengue virus 4]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Basavannacharya C]]
[[Category: Chan KWK]]
[[Category: Chan SA]]
[[Category: Lescar J]]
[[Category: Luo D]]
[[Category: Phoo WW]]
[[Category: Singh D]]
[[Category: Swarbrick CMD]]
[[Category: Vasudevan SG]]
[[Category: Wei N]]