6izz: Difference between revisions

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== Structural highlights ==

<table><tr><td colspan='2'>[[6izz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IZZ OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=6IZZ FirstGlance]. <br>

<table><tr><td colspan='2'>[[6izz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_3 Dengue virus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IZZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6IZZ FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B5C:2-oxo-2H-1,3-benzoxathiol-5-yl+acetate'>B5C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B5C:2-oxo-2H-1,3-benzoxathiol-5-yl+acetate'>B5C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6izz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6izz OCA], [http://pdbe.org/6izz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6izz RCSB], [http://www.ebi.ac.uk/pdbsum/6izz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6izz ProSAT]</span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6izz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6izz OCA], [http://pdbe.org/6izz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6izz RCSB], [http://www.ebi.ac.uk/pdbsum/6izz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6izz ProSAT]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

Dengue is a mosquito-borne viral infection that has spread globally in recent years. Around half of the world's population, especially in the tropics and subtropics, is at risk of infection. Every year, 50-100 million clinical cases are reported, and more than 500,000 patients develop the symptoms of severe dengue infection: dengue haemorrhagic fever and dengue shock syndrome, which threaten life in Asia and Latin America. No antiviral drug for dengue is available. The dengue virus (DENV) non-structural protein 5 (NS5), which possesses the RNA-dependent RNA polymerase (RdRp) activity and is responsible for viral replication and transcription, is an attractive target for anti-dengue drug development. In the present study, 16,240 small-molecule compounds in a fragment library were screened for their capabilities to inhibit the DENV type 2 (DENV2) RdRp activities in vitro. Based on in cellulo antiviral and cytotoxity assays, we selected the compound RK-0404678 with the EC50 value of 6.0 muM for DENV2. Crystallographic analyses revealed two unique binding sites for RK-0404678 within the RdRp, which are conserved in flavivirus NS5 proteins. No resistant viruses emerged after nine rounds of serial passage of DENV2 in the presence of RK-0404678, suggesting the high genetic barrier of this compound to the emergence of a resistant virus. Collectively, RK-0404678 and its binding sites provide a new framework for antiviral drug development.

Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase.,Shimizu H, Saito A, Mikuni J, Nakayama EE, Koyama H, Honma T, Shirouzu M, Sekine SI, Shioda T PLoS Negl Trop Dis. 2019 Nov 18;13(11):e0007894. doi:, 10.1371/journal.pntd.0007894. eCollection 2019 Nov. PMID:31738758<ref>PMID:31738758</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Dengue virus 3]]

[[Category: Large Structures]]

[[Category: Sekine, S]]

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@@ Line 3: / Line 3: @@
 <StructureSection load='6izz' size='340' side='right'caption='[[6izz]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6izz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IZZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IZZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6izz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Dengue_virus_3 Dengue virus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IZZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6IZZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B5C:2-oxo-2H-1,3-benzoxathiol-5-yl+acetate'>B5C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B5C:2-oxo-2H-1,3-benzoxathiol-5-yl+acetate'>B5C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6izz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6izz OCA], [http://pdbe.org/6izz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6izz RCSB], [http://www.ebi.ac.uk/pdbsum/6izz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6izz ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6izz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6izz OCA], [http://pdbe.org/6izz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6izz RCSB], [http://www.ebi.ac.uk/pdbsum/6izz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6izz ProSAT]</span></td></tr>
 </table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Dengue is a mosquito-borne viral infection that has spread globally in recent years. Around half of the world's population, especially in the tropics and subtropics, is at risk of infection. Every year, 50-100 million clinical cases are reported, and more than 500,000 patients develop the symptoms of severe dengue infection: dengue haemorrhagic fever and dengue shock syndrome, which threaten life in Asia and Latin America. No antiviral drug for dengue is available. The dengue virus (DENV) non-structural protein 5 (NS5), which possesses the RNA-dependent RNA polymerase (RdRp) activity and is responsible for viral replication and transcription, is an attractive target for anti-dengue drug development. In the present study, 16,240 small-molecule compounds in a fragment library were screened for their capabilities to inhibit the DENV type 2 (DENV2) RdRp activities in vitro. Based on in cellulo antiviral and cytotoxity assays, we selected the compound RK-0404678 with the EC50 value of 6.0 muM for DENV2. Crystallographic analyses revealed two unique binding sites for RK-0404678 within the RdRp, which are conserved in flavivirus NS5 proteins. No resistant viruses emerged after nine rounds of serial passage of DENV2 in the presence of RK-0404678, suggesting the high genetic barrier of this compound to the emergence of a resistant virus. Collectively, RK-0404678 and its binding sites provide a new framework for antiviral drug development.
+Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase.,Shimizu H, Saito A, Mikuni J, Nakayama EE, Koyama H, Honma T, Shirouzu M, Sekine SI, Shioda T PLoS Negl Trop Dis. 2019 Nov 18;13(11):e0007894. doi:, 10.1371/journal.pntd.0007894. eCollection 2019 Nov. PMID:31738758<ref>PMID:31738758</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6izz" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Dengue virus 3]]
 [[Category: Large Structures]]
 [[Category: Sekine, S]]