3cde

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[[Image:3cde.png|left|200px]]
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==Crystal structure of HCV NS5B polymerase with a novel Pyridazinone inhibitor==
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<StructureSection load='3cde' size='340' side='right' caption='[[3cde]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3cde]] is a 2 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=3CDE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CDE FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N3H:N-{3-[5-HYDROXY-2-(3-METHYLBUTYL)-3-OXO-6-THIOPHEN-2-YL-2,3-DIHYDROPYRIDAZIN-4-YL]-1,1-DIOXIDO-2H-1,2,4-BENZOTHIADIAZIN-7-YL}METHANESULFONAMIDE'>N3H</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bsc|3bsc]], [[3br9|3br9]], [[3bsa|3bsa]]</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=3cde FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cde OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cde RCSB], [http://www.ebi.ac.uk/pdbsum/3cde 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/cd/3cde_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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5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. Lead optimization led to the discovery of compound 3a, which displayed potent inhibitory activities in biochemical and replicon assays [IC(50) (1b)&lt;10nM; IC(50) (1a)=22 nM; EC(50) (1b)=5nM], good stability toward human liver microsomes (HLM t(1/2)&gt;60 min), and high ratios of liver to plasma concentrations 12h after a single oral administration to rats.
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{{STRUCTURE_3cde| PDB=3cde | SCENE= }}
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Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)- 5-hydroxy-2H-pyridazin-3-ones. Part 3: Further optimization of the 2-, 6-, and 7'-substituents and initial pharmacokinetic assessments.,Li LS, Zhou Y, Murphy DE, Stankovic N, Zhao J, Dragovich PS, Bertolini T, Sun Z, Ayida B, Tran CV, Ruebsam F, Webber SE, Shah AM, Tsan M, Showalter RE, Patel R, Lebrun LA, Bartkowski DM, Nolan TG, Norris DA, Kamran R, Brooks J, Sergeeva MV, Kirkovsky L, Zhao Q, Kissinger CR Bioorg Med Chem Lett. 2008 Jun 1;18(11):3446-55. Epub 2008 Mar 5. PMID:18457949<ref>PMID:18457949</ref>
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===Crystal structure of HCV NS5B polymerase with a novel Pyridazinone inhibitor===
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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_18457949}}
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==About this Structure==
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[[3cde]] is a 2 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=3CDE 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:018457949</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 06:23, 29 September 2014

Crystal structure of HCV NS5B polymerase with a novel Pyridazinone inhibitor

3cde, resolution 2.10Å

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