4oks - Revision history

OCA at 12:40, 1 March 2024

OCA — Fri, 01 Mar 2024 12:40:45 GMT

←Older revision		Revision as of 12:40, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4oks]] 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=4OKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OKS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4oks]] 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=4OKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OKS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2T9:[6-(3,5-DIAMINOPHENYL)-1-(2-METHOXY-5-NITROBENZYL)-1H-INDOL-3-YL]ACETIC+ACID'>2T9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.25Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2T9:[6-(3,5-DIAMINOPHENYL)-1-(2-METHOXY-5-NITROBENZYL)-1H-INDOL-3-YL]ACETIC+ACID'>2T9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [https://pdbe.org/4oks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [https://www.ebi.ac.uk/pdbsum/4oks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oks ProSAT]</span></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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [https://pdbe.org/4oks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [https://www.ebi.ac.uk/pdbsum/4oks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oks ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/K4KA16_9HEPC K4KA16_9HEPC]		[https://www.uniprot.org/uniprot/K4KA16_9HEPC K4KA16_9HEPC]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Future treatments for individuals infected by the hepatitis C virus (HCV) will likely involve combinations of compounds that inhibit multiple viral targets. The helicase of HCV is an attractive target with no known drug candidates in clinical trials. Herein we describe an integrated strategy for identifying fragment inhibitors using structural and biophysical techniques. Based on an X-ray structure of apo HCV helicase and in silico and bioinformatic analyses of HCV variants, we identified that one site in particular (labeled 3 + 4) was the most conserved and attractive pocket to target for a drug discovery campaign. Compounds from multiple sources were screened to identify inhibitors or binders to this site, and enzymatic and biophysical assays (NMR and SPR) were used to triage the most promising ligands for 3D structure determination by X-ray crystallography. Medicinal chemistry and biophysical evaluations focused on exploring the most promising lead series. The strategies employed here can have general utility in drug discovery.
-
-	Integrated strategies for identifying leads that target the NS3 helicase of the hepatitis C virus.,Laplante SR, Padyana AK, Abeywardane A, Bonneau P, Cartier M, Coulombe R, Jakalian A, Wildeson-Jones J, Li X, Liang S, McKercher G, White P, Zhang Q, Taylor SJ J Med Chem. 2014 Mar 13;57(5):2074-90. doi: 10.1021/jm401432c. Epub 2014 Jan 27. PMID:24467709<ref>PMID:24467709</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4oks" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
		+	*[[Helicase 3D structures\|Helicase 3D structures]]
	*[[Virus protease 3D structures\|Virus protease 3D structures]]		*[[Virus protease 3D structures\|Virus protease 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:30, 25 January 2023

OCA — Wed, 25 Jan 2023 07:30:50 GMT

←Older revision		Revision as of 07:30, 25 January 2023
Line 1:		Line 1:

	==Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]==		==Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]==
-	<StructureSection load='4oks' size='340' side='right' caption='[[4oks]], [[Resolution\|resolution]] 2.25Å' scene=''>	+	<StructureSection load='4oks' size='340' side='right'caption='[[4oks]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4oks]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~9hepc 9hepc~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OKS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4OKS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4oks]] 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=4OKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OKS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2T9:[6-(3,5-DIAMINOPHENYL)-1-(2-METHOXY-5-NITROBENZYL)-1H-INDOL-3-YL]ACETIC+ACID'>2T9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2T9:[6-(3,5-DIAMINOPHENYL)-1-(2-METHOXY-5-NITROBENZYL)-1H-INDOL-3-YL]ACETIC+ACID'>2T9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ojq\|4ojq]], [[4ok3\|4ok3]], [[4ok5\|4ok5]], [[4ok6\|4ok6]]</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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [https://pdbe.org/4oks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [https://www.ebi.ac.uk/pdbsum/4oks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oks ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])~~</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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [~~http~~://pdbe.org/4oks PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4oks PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4oks ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/K4KA16_9HEPC K4KA16_9HEPC]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4oks" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4oks" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Virus protease 3D structures\|Virus protease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Padyana, A K~~]]	+	[[Category: Hepacivirus C]]
-	[[Category: ~~Atpase~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Hepatitis]]~~	+	[[Category: Padyana AK]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Ns3 helicase]]~~	+
-	~~[[Category: Ntpase~~]]	+

OCA at 17:42, 11 August 2016

OCA — Thu, 11 Aug 2016 17:42:06 GMT

←Older revision		Revision as of 17:42, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]==		==Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]==
	<StructureSection load='4oks' size='340' side='right' caption='[[4oks]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='4oks' size='340' side='right' caption='[[4oks]], [[Resolution\|resolution]] 2.25Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ojq\|4ojq]], [[4ok3\|4ok3]], [[4ok5\|4ok5]], [[4ok6\|4ok6]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ojq\|4ojq]], [[4ok3\|4ok3]], [[4ok5\|4ok5]], [[4ok6\|4ok6]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])</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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [http://www.ebi.ac.uk/pdbsum/4oks PDBsum]</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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [http://pdbe.org/4oks PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [http://www.ebi.ac.uk/pdbsum/4oks PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oks ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 16:		Line 17:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4oks" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:29, 5 January 2015

OCA — Mon, 05 Jan 2015 08:29:25 GMT

←Older revision		Revision as of 08:29, 5 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4oks]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OKS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OKS FirstGlance]. <br>		<table><tr><td colspan='2'>[[4oks]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OKS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OKS FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2T9:[6-(3,5-DIAMINOPHENYL)-1-(2-METHOXY-5-NITROBENZYL)-1H-INDOL-3-YL]ACETIC+ACID'>2T9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2T9:[6-(3,5-DIAMINOPHENYL)-1-(2-METHOXY-5-NITROBENZYL)-1H-INDOL-3-YL]ACETIC+ACID'>2T9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ojq\|4ojq]], [[4ok3\|4ok3]], [[4ok5\|4ok5]], [[4ok6\|4ok6]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ojq\|4ojq]], [[4ok3\|4ok3]], [[4ok5\|4ok5]], [[4ok6\|4ok6]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])</td></tr>
-	<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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [http://www.ebi.ac.uk/pdbsum/4oks PDBsum]</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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [http://www.ebi.ac.uk/pdbsum/4oks PDBsum]</span></td></tr>
-	<table>	+	</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 14:		Line 14:
	Integrated strategies for identifying leads that target the NS3 helicase of the hepatitis C virus.,Laplante SR, Padyana AK, Abeywardane A, Bonneau P, Cartier M, Coulombe R, Jakalian A, Wildeson-Jones J, Li X, Liang S, McKercher G, White P, Zhang Q, Taylor SJ J Med Chem. 2014 Mar 13;57(5):2074-90. doi: 10.1021/jm401432c. Epub 2014 Jan 27. PMID:24467709<ref>PMID:24467709</ref>		Integrated strategies for identifying leads that target the NS3 helicase of the hepatitis C virus.,Laplante SR, Padyana AK, Abeywardane A, Bonneau P, Cartier M, Coulombe R, Jakalian A, Wildeson-Jones J, Li X, Liang S, McKercher G, White P, Zhang Q, Taylor SJ J Med Chem. 2014 Mar 13;57(5):2074-90. doi: 10.1021/jm401432c. Epub 2014 Jan 27. PMID:24467709<ref>PMID:24467709</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, a database of the U.S. National Library of Medicine.<br>	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
	== References ==		== References ==
Line 20:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	~~[[Category: 9hepc]]~~	+	[[Category: Padyana, A K]]
-	[[Category: Padyana, A K.]]	+
	[[Category: Atpase]]		[[Category: Atpase]]
	[[Category: Hepatitis]]		[[Category: Hepatitis]]

OCA at 12:40, 18 May 2014

OCA — Sun, 18 May 2014 12:40:09 GMT

←Older revision		Revision as of 12:40, 18 May 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4oks\| PDB=4oks \| SCENE= }}~~	+	==Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]==
-	===Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]===	+	<StructureSection load='4oks' size='340' side='right' caption='[[4oks]], [[Resolution\|resolution]] 2.25Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24467709}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4oks]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OKS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OKS FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2T9:[6-(3,5-DIAMINOPHENYL)-1-(2-METHOXY-5-NITROBENZYL)-1H-INDOL-3-YL]ACETIC+ACID'>2T9</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ojq\|4ojq]], [[4ok3\|4ok3]], [[4ok5\|4ok5]], [[4ok6\|4ok6]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11103 9HEPC])</td></tr>
		+	<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=4oks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oks OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oks RCSB], [http://www.ebi.ac.uk/pdbsum/4oks PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Future treatments for individuals infected by the hepatitis C virus (HCV) will likely involve combinations of compounds that inhibit multiple viral targets. The helicase of HCV is an attractive target with no known drug candidates in clinical trials. Herein we describe an integrated strategy for identifying fragment inhibitors using structural and biophysical techniques. Based on an X-ray structure of apo HCV helicase and in silico and bioinformatic analyses of HCV variants, we identified that one site in particular (labeled 3 + 4) was the most conserved and attractive pocket to target for a drug discovery campaign. Compounds from multiple sources were screened to identify inhibitors or binders to this site, and enzymatic and biophysical assays (NMR and SPR) were used to triage the most promising ligands for 3D structure determination by X-ray crystallography. Medicinal chemistry and biophysical evaluations focused on exploring the most promising lead series. The strategies employed here can have general utility in drug discovery.

-	~~==About this Structure==~~	+	Integrated strategies for identifying leads that target the NS3 helicase of the hepatitis C virus.,Laplante SR, Padyana AK, Abeywardane A, Bonneau P, Cartier M, Coulombe R, Jakalian A, Wildeson-Jones J, Li X, Liang S, McKercher G, White P, Zhang Q, Taylor SJ J Med Chem. 2014 Mar 13;57(5):2074-90. doi: 10.1021/jm401432c. Epub 2014 Jan 27. PMID:24467709<ref>PMID:24467709</ref>
-	~~[[4oks]] is a 2 chain structure~~. ~~Full crystallographic information is available from [http~~:~~//oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4OKS OCA]~~.	+

-	==~~Reference~~==	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024467709</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: 9hepc]]
	[[Category: Padyana, A K.]]		[[Category: Padyana, A K.]]
	[[Category: Atpase]]		[[Category: Atpase]]

OCA at 07:11, 2 April 2014

OCA — Wed, 02 Apr 2014 07:11:57 GMT

←Older revision		Revision as of 07:11, 2 April 2014
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4oks\| PDB=4oks \| SCENE= }}
		+	===Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]===
		+	{{ABSTRACT_PUBMED_24467709}}

-	~~The entry~~ 4oks is ~~ON HOLD until Mar 16 2015~~	+	==About this Structure==
		+	[[4oks]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OKS OCA].

-	~~Authors~~: Padyana, A.K.	+	==Reference==
-		+	<ref group="xtra">PMID:024467709</ref><references group="xtra"/><references/>
-	~~Description~~: ~~Crystal Structure of~~ Hepatitis ~~C Virus NS3 Helicase Inhibitor Co~~-complex ~~with Compound 19~~ [[~~6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl~~]~~acetic acid~~]	+	[[Category: Padyana, A K.]]
		+	[[Category: Atpase]]
		+	[[Category: Hepatitis]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Ns3 helicase]]
		+	[[Category: Ntpase]]

OCA at 16:46, 3 March 2014

OCA — Mon, 03 Mar 2014 16:46:35 GMT

←Older revision		Revision as of 16:46, 3 March 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4oks is ON HOLD	+	The entry 4oks is ON HOLD until Mar 16 2015

	Authors: Padyana, A.K.		Authors: Padyana, A.K.

	Description: Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]		Description: Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]

OCA at 10:31, 5 February 2014

OCA — Wed, 05 Feb 2014 10:31:06 GMT

←Older revision		Revision as of 10:31, 5 February 2014
Line 5:		Line 5:
	Authors: Padyana, A.K.		Authors: Padyana, A.K.

-	Description: Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19	+	Description: Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19 [[6-(3,5-diaminophenyl)-1-(2-methoxy-5-nitrobenzyl)-1H-indol-3-yl]acetic acid]

OCA: Protected "4oks" [edit=sysop:move=sysop]

OCA — Wed, 29 Jan 2014 07:12:24 GMT

Protected "4oks" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:12, 29 January 2014

OCA: New page: '''Unreleased structure''' The entry 4oks is ON HOLD Authors: Padyana, A.K. Description: Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19

OCA — Wed, 29 Jan 2014 07:12:23 GMT

New page: '''Unreleased structure''' The entry 4oks is ON HOLD Authors: Padyana, A.K. Description: Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19

New page

'''Unreleased structure'''

The entry 4oks is ON HOLD

Authors: Padyana, A.K.

Description: Crystal Structure of Hepatitis C Virus NS3 Helicase Inhibitor Co-complex with Compound 19