2whx: Difference between revisions

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-[[Image:2whx.png|left|200px]]
+==A SECOND CONFORMATION OF THE NS3 PROTEASE-HELICASE FROM DENGUE VIRUS==
+<StructureSection load='2whx' size='340' side='right' caption='[[2whx]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2whx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_4 Dengue virus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WHX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WHX FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jlx|2jlx]], [[2jlq|2jlq]], [[2jlw|2jlw]], [[2jlu|2jlu]], [[2jlv|2jlv]], [[2jlr|2jlr]], [[2jls|2jls]], [[2jlz|2jlz]], [[2jly|2jly]], [[2wzq|2wzq]]</td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2whx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2whx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2whx RCSB], [http://www.ebi.ac.uk/pdbsum/2whx PDBsum]</span></td></tr>
+<table>
+== 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/wh/2whx_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/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The dengue virus (DENV) NS3 protein is essential for viral polyprotein processing and RNA replication. It contains an N-terminal serine protease region (residues 1-168) joined to an RNA helicase (residues 180-618) by an 11-amino acid linker (169-179). The structure at 3.15 A of the soluble NS3 protein from DENV4 covalently attached to 18 residues of the NS2B cofactor region (NS2B(18)NS3) revealed an elongated molecule with the protease domain abutting subdomains I and II of the helicase (Luo, D., Xu, T., Hunke, C., Gruber, G., Vasudevan, S. G., and Lescar, J. (2008) J. Virol. 82, 173-183). Unexpectedly, using similar crystal growth conditions, we observed an alternative conformation where the protease domain has rotated by approximately 161 degrees with respect to the helicase domain. We report this new crystal structure bound to ADP-Mn(2+) refined to a resolution of 2.2 A. The biological significance for interdomain flexibility conferred by the linker region was probed by either inserting a Gly residue between Glu(173) and Pro(174) or replacing Pro(174) with a Gly residue. Both mutations resulted in significantly lower ATPase and helicase activities. We next increased flexibility in the linker by introducing a Pro(176) to Gly mutation in a DENV2 replicon system. A 70% reduction in luciferase reporter signal and a similar reduction in the level of viral RNA synthesis were observed. Our results indicate that the linker region has evolved to an optimum length to confer flexibility to the NS3 protein that is required both for polyprotein processing and RNA replication.
-{{STRUCTURE_2whx|  PDB=2whx  |  SCENE=  }}
+Flexibility between the protease and helicase domains of the dengue virus NS3 protein conferred by the linker region and its functional implications.,Luo D, Wei N, Doan DN, Paradkar PN, Chong Y, Davidson AD, Kotaka M, Lescar J, Vasudevan SG J Biol Chem. 2010 Jun 11;285(24):18817-27. Epub 2010 Apr 7. PMID:20375022<ref>PMID:20375022</ref>
-===A SECOND CONFORMATION OF THE NS3 PROTEASE-HELICASE FROM DENGUE VIRUS===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_20375022}}
-==About this Structure==
-[[2whx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_4 Dengue virus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WHX OCA].
 ==See Also==
+*[[Helicase|Helicase]]
 *[[Virus protease|Virus protease]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020375022</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Dengue virus 4]]
 [[Category: Lescar, J.]]