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==Structure of a Proline Sulfonamide Inhibitor Bound to HCV NS5b Polymerase== | |||
<StructureSection load='2gc8' size='340' side='right'caption='[[2gc8]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
| | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2gc8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GC8 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]] 2.2Å</td></tr> | |||
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=885:1-[(2-AMINO-4-CHLORO-5-METHYLPHENYL)SULFONYL]-L-PROLINE'>885</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=2gc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gc8 OCA], [https://pdbe.org/2gc8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gc8 RCSB], [https://www.ebi.ac.uk/pdbsum/2gc8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gc8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q99AU2_9HEPC Q99AU2_9HEPC] | |||
== Evolutionary Conservation == | |||
== | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gc/2gc8_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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/main_output.php?pdb_ID=2gc8 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail. | Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail. | ||
Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site.,Gopalsamy A, Chopra R, Lim K, Ciszewski G, Shi M, Curran KJ, Sukits SF, Svenson K, Bard J, Ellingboe JW, Agarwal A, Krishnamurthy G, Howe AY, Orlowski M, Feld B, O'Connell J, Mansour TS J Med Chem. 2006 Jun 1;49(11):3052-5. PMID:16722622<ref>PMID:16722622</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2gc8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hepacivirus C]] | |||
[[Category: Large Structures]] | |||
[[Category: Agarwal A]] | |||
[[Category: Bard J]] | |||
[[Category: Chopra R]] | |||
[[Category: Ciszewski G]] | |||
[[Category: Curran KJ]] | |||
[[Category: Ellingboe JW]] | |||
[[Category: Feld B]] | |||
[[Category: Gopalsamy A]] | |||
[[Category: Howe AY]] | |||
[[Category: Krishnamurthy G]] | |||
[[Category: Lim K]] | |||
[[Category: Mansour TS]] | |||
[[Category: O'connell J]] | |||
[[Category: Orlowski M]] | |||
[[Category: Shi M]] | |||
[[Category: Sukits SF]] | |||
[[Category: Svenson K]] | |||
Latest revision as of 12:38, 30 August 2023
Structure of a Proline Sulfonamide Inhibitor Bound to HCV NS5b PolymeraseStructure of a Proline Sulfonamide Inhibitor Bound to HCV NS5b Polymerase
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThrough high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail. Discovery of proline sulfonamides as potent and selective hepatitis C virus NS5b polymerase inhibitors. Evidence for a new NS5b polymerase binding site.,Gopalsamy A, Chopra R, Lim K, Ciszewski G, Shi M, Curran KJ, Sukits SF, Svenson K, Bard J, Ellingboe JW, Agarwal A, Krishnamurthy G, Howe AY, Orlowski M, Feld B, O'Connell J, Mansour TS J Med Chem. 2006 Jun 1;49(11):3052-5. PMID:16722622[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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