3vqs: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:3vqs.jpg|left|200px]]
-{{STRUCTURE_3vqs|  PDB=3vqs  |  SCENE=  }}
+==Crystal structure of HCV NS5B RNA polymerase with a novel piperazine inhibitor==
+<StructureSection load='3vqs' size='340' side='right'caption='[[3vqs]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3vqs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_hominis Hepacivirus hominis]. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</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='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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+JTK-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.
-===Crystal structure of HCV NS5B RNA polymerase with a novel piperazine inhibitor===
+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<ref>PMID:22615294</ref>
-{{ABSTRACT_PUBMED_22615294}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3vqs" style="background-color:#fffaf0;"></div>
-==About this Structure==
+==See Also==
-[[3vqs]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus Hepatitis c virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VQS OCA].
+*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:022615294</ref><references group="xtra"/>
+__TOC__
-[[Category: Hepatitis c virus]]
+</StructureSection>
-[[Category: Adachi, T.]]
+[[Category: Hepacivirus hominis]]
-[[Category: Ando, I.]]
+[[Category: Large Structures]]
-[[Category: Doi, S.]]
+[[Category: Adachi T]]
-[[Category: Kamada, M.]]
+[[Category: Ando I]]
-[[Category: Nomura, A.]]
+[[Category: Doi S]]
-[[Category: Orita, T.]]
+[[Category: Kamada M]]
-[[Category: Sugimoto, K.]]
+[[Category: Nomura A]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
+[[Category: Orita T]]
-[[Category: Rna-dependent rna polymerase]]
+[[Category: Sugimoto K]]