3q0z
From Proteopedia
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| - | [[ | + | ==Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase complex with (2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5h-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid== |
| + | <StructureSection load='3q0z' size='340' side='right' caption='[[3q0z]], [[Resolution|resolution]] 2.29Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3q0z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_c_virus_subtype_1b Hepatitis c virus subtype 1b]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q0Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q0Z FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=23E:(2E)-3-(4-{[(1-{[(13-CYCLOHEXYL-6-OXO-6,7-DIHYDRO-5H-INDOLO[1,2-D][1,4]BENZODIAZEPIN-10-YL)CARBONYL]AMINO}CYCLOPENTYL)CARBONYL]AMINO}PHENYL)PROP-2-ENOIC+ACID'>23E</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=31647 Hepatitis C virus subtype 1b])</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=3q0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q0z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q0z RCSB], [http://www.ebi.ac.uk/pdbsum/3q0z PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Herein, we present initial SAR studies on a series of bridged 2-arylindole-based NS5B inhibitors. The introduction of bridging elements between the indole N1 and the ortho-position of the 2-aryl moiety resulted in conformationally constrained heterocycles that possess multiple additional vectors for further exploration. The binding mode and pharmacokinetic (PK) properties of select examples, including: 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-d][1,4]benzodiazepine-10-car boxylic acid (7) (IC(50)=0.07muM, %F=18), are reported. | ||
| - | + | Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus.,Zheng X, Hudyma TW, Martin SW, Bergstrom C, Ding M, He F, Romine J, Poss MA, Kadow JF, Chang CH, Wan J, Witmer MR, Morin P, Camac DM, Sheriff S, Beno BR, Rigat KL, Wang YK, Fridell R, Lemm J, Qiu D, Liu M, Voss S, Pelosi L, Roberts SB, Gao M, Knipe J, Gentles RG Bioorg Med Chem Lett. 2011 Mar 23. PMID:21486696<ref>PMID:21486696</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[RNA polymerase|RNA polymerase]] | *[[RNA polymerase|RNA polymerase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Hepatitis c virus subtype 1b]] | [[Category: Hepatitis c virus subtype 1b]] | ||
[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
| - | [[Category: Sheriff, S | + | [[Category: Sheriff, S]] |
[[Category: Finger]] | [[Category: Finger]] | ||
[[Category: Hcv]] | [[Category: Hcv]] | ||
Revision as of 11:03, 9 December 2014
Crystal structure of the hepatitis C virus NS5B RNA-dependent RNA polymerase complex with (2E)-3-(4-{[(1-{[(13-cyclohexyl-6-oxo-6,7-dihydro-5h-indolo[1,2-d][1,4]benzodiazepin-10-yl)carbonyl]amino}cyclopentyl)carbonyl]amino}phenyl)prop-2-enoic acid
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