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| | ==HCV NS5B GT1A C316Y with GSK5852== | | ==HCV NS5B GT1A C316Y with GSK5852== |
| - | <StructureSection load='4khr' size='340' side='right' caption='[[4khr]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='4khr' size='340' side='right'caption='[[4khr]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4khr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1a Hepatitis c virus subtype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KHR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KHR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4khr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_C_virus_genotype_1a Hepatitis C virus genotype 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KHR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PV:[4-({[5-CYCLOPROPYL-2-(4-FLUOROPHENYL)-3-(METHYLCARBAMOYL)-1-BENZOFURAN-6-YL](METHYLSULFONYL)AMINO}METHYL)-2-FLUOROPHENYL]BORONIC+ACID'>1PV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PV:[4-({[5-CYCLOPROPYL-2-(4-FLUOROPHENYL)-3-(METHYLCARBAMOYL)-1-BENZOFURAN-6-YL](METHYLSULFONYL)AMINO}METHYL)-2-FLUOROPHENYL]BORONIC+ACID'>1PV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kai|4kai]], [[4kb7|4kb7]], [[4kbi|4kbi]], [[4ke5|4ke5]], [[4khm|4khm]]</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=4khr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4khr OCA], [https://pdbe.org/4khr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4khr RCSB], [https://www.ebi.ac.uk/pdbsum/4khr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4khr ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NS5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31646 Hepatitis C virus subtype 1a])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></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=4khr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4khr OCA], [http://pdbe.org/4khr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4khr RCSB], [http://www.ebi.ac.uk/pdbsum/4khr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4khr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/B1PPP0_9HEPC B1PPP0_9HEPC] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4khr" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4khr" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hepatitis c virus subtype 1a]] | + | [[Category: Hepatitis C virus genotype 1a]] |
| - | [[Category: RNA-directed RNA polymerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kahler, K M]] | + | [[Category: Kahler KM]] |
| - | [[Category: Shotwell, J B]] | + | [[Category: Shotwell JB]] |
| - | [[Category: Williams, S P]] | + | [[Category: Williams SP]] |
| - | [[Category: Boron]]
| + | |
| - | [[Category: Hcv ns5b]]
| + | |
| - | [[Category: Hcv polymerase]]
| + | |
| - | [[Category: P66]]
| + | |
| - | [[Category: P70]]
| + | |
| - | [[Category: Polymerase]]
| + | |
| - | [[Category: Replication-replication inhibitor complex]]
| + | |
| - | [[Category: Rna dependent rna polymerase]]
| + | |
| - | [[Category: Rna directed rna polymerase]]
| + | |
| - | [[Category: Rns dependent rna polymerase]]
| + | |
| - | [[Category: Site iv inhibitor]]
| + | |
| Structural highlights
Function
B1PPP0_9HEPC
Publication Abstract from PubMed
A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a sub-genomic replication system for a series of non-nucleoside boron-containing HCV RNA-Dependent RNA Polymerase (NS5B) inhibitors are described. A summary of the discovery of GSK5852 (3), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.
Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase.,Maynard A, Crosby RM, Ellis B, Hamatake R, Hong Z, Johns BA, Kahler KM, Koble C, Leivers AL, Leivers MR, Mathis A, Peat AJ, Pouliot JJ, Roberts CD, Samano V, Schmidt RM, Smith GK, Spaltenstein A, Stewart EL, Thommes P, Turner EM, Voitenleitner C, Walker JT, Waitt G, Weatherhead J, Weaver KL, Williams S, Wright L, Xiong ZZ, Haigh D, Shotwell JB J Med Chem. 2013 May 14. PMID:23672667[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Maynard A, Crosby RM, Ellis B, Hamatake R, Hong Z, Johns BA, Kahler KM, Koble C, Leivers AL, Leivers MR, Mathis A, Peat AJ, Pouliot JJ, Roberts CD, Samano V, Schmidt RM, Smith GK, Spaltenstein A, Stewart EL, Thommes P, Turner EM, Voitenleitner C, Walker JT, Waitt G, Weatherhead J, Weaver KL, Williams S, Wright L, Xiong ZZ, Haigh D, Shotwell JB. Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase. J Med Chem. 2013 May 14. PMID:23672667 doi:10.1021/jm400317w
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