3frz

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[[Image:3frz.png|left|200px]]
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==Crystal Structure of HCV NS5B RNA polymerase in complex with PF868554==
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<StructureSection load='3frz' size='340' side='right' caption='[[3frz]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3frz]] is a 1 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=3FRZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FRZ FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AG0:(6R)-6-CYCLOPENTYL-6-[2-(2,6-DIETHYLPYRIDIN-4-YL)ETHYL]-3-[(5,7-DIMETHYL[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-2-YL)METHYL]-4-HYDROXY-5,6-DIHYDRO-2H-PYRAN-2-ONE'>AG0</scene>, <scene name='pdbligand=AG6:N-[(BENZYLOXY)CARBONYL]-L-ALPHA-GLUTAMYL-N-[(1S)-4-OXO-4-PHENYL-1-PROPYLBUT-2-EN-1-YL]-L-PHENYLALANINAMIDE'>AG6</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hai|2hai]], [[1os5|1os5]]</td></tr>
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<tr><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=11103 Hepatitis C virus])</td></tr>
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<tr><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>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3frz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3frz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3frz RCSB], [http://www.ebi.ac.uk/pdbsum/3frz PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fr/3frz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The HCV RNA-dependent RNA polymerase has emerged as one of the key targets for novel anti-HCV therapy development. Herein, we report the optimization of the dihydropyrone series inhibitors to improve compound aqueous solubility and reduce CYP2D6 inhibition, which led to the discovery of compound 24 (PF-00868554). Compound 24 is a potent and selective HCV polymerase inhibitor with a favorable pharmacokinetic profile and has recently entered a phase II clinical evaluation in patients with genotype 1 HCV.
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{{STRUCTURE_3frz| PDB=3frz | SCENE= }}
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Discovery of (R)-6-Cyclopentyl-6-(2-(2,6-diethylpyridin-4-yl)ethyl)-3-((5,7-dimethyl-[1 ,2,4]triazolo[1,5-a]pyrimidin-2-yl)methyl)-4-hydroxy-5,6-dihydropyran-2-on e (PF-00868554) as a Potent and Orally Available Hepatitis C Virus Polymerase Inhibitor.,Li H, Tatlock J, Linton A, Gonzalez J, Jewell T, Patel L, Ludlum S, Drowns M, Rahavendran SV, Skor H, Hunter R, Shi ST, Herlihy KJ, Parge H, Hickey M, Yu X, Chau F, Nonomiya J, Lewis C J Med Chem. 2009 Feb 11. PMID:19209845<ref>PMID:19209845</ref>
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===Crystal Structure of HCV NS5B RNA polymerase in complex with PF868554===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_19209845}}
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==About this Structure==
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[[3frz]] is a 1 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=3FRZ OCA].
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==See Also==
==See Also==
*[[RNA polymerase|RNA polymerase]]
*[[RNA polymerase|RNA polymerase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019209845</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Hepatitis c virus]]
[[Category: Hepatitis c virus]]
[[Category: RNA-directed RNA polymerase]]
[[Category: RNA-directed RNA polymerase]]

Revision as of 12:10, 29 September 2014

Crystal Structure of HCV NS5B RNA polymerase in complex with PF868554

3frz, resolution 1.86Å

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