6mo2: Difference between revisions

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-'''Unreleased structure'''
-The entry 6mo2 is ON HOLD
+==Structure of dengue virus protease with an allosteric Inhibitor that blocks replication==
+<StructureSection load='6mo2' size='340' side='right'caption='[[6mo2]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6mo2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MO2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MO2 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JVM:1-(4-{5-[(piperidin-4-yl)methoxy]-3-[4-(1H-pyrazol-4-yl)phenyl]pyrazin-2-yl}phenyl)methanamine'>JVM</scene></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=6mo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mo2 OCA], [http://pdbe.org/6mo2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mo2 RCSB], [http://www.ebi.ac.uk/pdbsum/6mo2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mo2 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Flaviviruses, including dengue, West Nile and recently emerged Zika virus, are important human pathogens, but there are no drugs to prevent or treat these viral infections. The highly conserved Flavivirus NS2B-NS3 protease is essential for viral replication and therefore a drug target. Compound screening followed by medicinal chemistry yielded a series of drug-like, broadly active inhibitors of Flavivirus proteases with IC50 as low as 120 nM. The inhibitor exhibited significant antiviral activities in cells (EC68: 300-600 nM) and in a mouse model of Zika virus infection. X-ray studies reveal that the inhibitors bind to an allosteric, mostly hydrophobic pocket of dengue NS3 and hold the protease in an open, catalytically inactive conformation. The inhibitors and their binding structures would be useful for rational drug development targeting Zika, dengue and other Flaviviruses.
-Authors:
+Discovery, X-ray Crystallography and Antiviral Activity of Allosteric Inhibitors of Flavivirus NS2B-NS3 Protease.,Yao Y, Huo T, Lin YL, Nie S, Wu F, Hua Y, Wu J, Kneubehl AR, Vogt MB, Rico-Hesse R, Song Y J Am Chem Soc. 2019 May 1;141(17):6832-6836. doi: 10.1021/jacs.9b02505. Epub 2019, Apr 23. PMID:31017399<ref>PMID:31017399</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6mo2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Dengue virus 2]]
+[[Category: Large Structures]]
+[[Category: Hua, Y]]
+[[Category: Huo, T]]
+[[Category: Lin, Y L]]
+[[Category: Nie, S]]
+[[Category: Song, Y]]
+[[Category: Wu, F]]
+[[Category: Wu, J]]
+[[Category: Yao, Y]]
+[[Category: Allosteric inhibitor]]
+[[Category: Complex]]
+[[Category: Inhibitor]]
+[[Category: Protease]]
+[[Category: Viral protein]]
+[[Category: Viral protein-inhibitor complex]]