3vqs: Difference between revisions
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==Crystal structure of HCV NS5B RNA polymerase with a novel piperazine inhibitor== | ==Crystal structure of HCV NS5B RNA polymerase with a novel piperazine inhibitor== | ||
<StructureSection load='3vqs' size='340' side='right' caption='[[3vqs]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='3vqs' size='340' side='right'caption='[[3vqs]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3vqs]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3vqs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VQS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=JT1:(2R)-4-(5-CYCLOPROPYL[1,3]THIAZOLO[4,5-D]PYRIMIDIN-2-YL)-N-[3-FLUORO-4-(TRIFLUOROMETHOXY)BENZYL]-1-{[4-(TRIFLUOROMETHYL)PHENYL]SULFONYL}PIPERAZINE-2-CARBOXAMIDE'>JT1</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=JT1:(2R)-4-(5-CYCLOPROPYL[1,3]THIAZOLO[4,5-D]PYRIMIDIN-2-YL)-N-[3-FLUORO-4-(TRIFLUOROMETHOXY)BENZYL]-1-{[4-(TRIFLUOROMETHYL)PHENYL]SULFONYL}PIPERAZINE-2-CARBOXAMIDE'>JT1</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1quv|1quv]], [[2dxs|2dxs]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1quv|1quv]], [[2dxs|2dxs]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">genotype 1b ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">genotype 1b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vqs OCA], [https://pdbe.org/3vqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vqs RCSB], [https://www.ebi.ac.uk/pdbsum/3vqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vqs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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==See Also== | ==See Also== | ||
*[[RNA polymerase|RNA polymerase]] | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Adachi, T]] | [[Category: Adachi, T]] | ||
[[Category: Ando, I]] | [[Category: Ando, I]] | ||
Revision as of 21:58, 27 July 2022
Crystal structure of HCV NS5B RNA polymerase with a novel piperazine inhibitorCrystal structure of HCV NS5B RNA polymerase with a novel piperazine inhibitor
Structural highlights
Publication Abstract from PubMedJTK-853 is a novel piperazine derivative nonnucleoside inhibitor of hepatitis C virus (HCV) RNA-dependent RNA polymerase. JTK-853 showed potent inhibitory activity against genotype 1 HCV polymerase, with a 50% inhibitory concentration in the nanomolar range, and showed potent antiviral activity against the genotype 1b replicon, with a 50% effective concentration of 0.035 muM. The presence of human serum at up to 40% had little effect on the antiviral activity of JTK-853. Structure analysis of HCV polymerase with JTK-853 revealed that JTK-853 associates with the palm site and beta-hairpin region of HCV polymerase, and JTK-853 showed decreased antiviral activity against HCV replicons bearing the resistance mutations C316Y, M414T, Y452H, and L466V in the palm site region of HCV polymerase. JTK-853 showed an additive combination effect with other DAAs (direct antiviral agents), such as nucleoside polymerase inhibitor, thumb pocket-binding nonnucleoside polymerase inhibitor, NS5A inhibitor, and protease inhibitor. Collectively, these data demonstrate that JTK-853 is a potent and novel nonnucleoside palm site-binding HCV polymerase inhibitor, suggesting JTK-853 as a potentially useful agent in combination with other DAAs for treatment of HCV infections. Preclinical Characterization of JTK-853, a Novel Nonnucleoside Inhibitor of the Hepatitis C Virus RNA-Dependent RNA Polymerase.,Ando I, Adachi T, Ogura N, Toyonaga Y, Sugimoto K, Abe H, Kamada M, Noguchi T Antimicrob Agents Chemother. 2012 Aug;56(8):4250-6. Epub 2012 May 21. PMID:22615294[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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