4ibi - Revision history

OCA at 14:27, 29 November 2023

2023-11-29T14:27:29Z

← Older revision		Revision as of 14:27, 29 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Mayinga,_Zaire,_1976 Ebola virus - Mayinga, Zaire, 1976]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IBI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Mayinga,_Zaire,_1976 Ebola virus - Mayinga, Zaire, 1976]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IBI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</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]] 1.473Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [https://pdbe.org/4ibi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [https://www.ebi.ac.uk/pdbsum/4ibi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibi 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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [https://pdbe.org/4ibi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [https://www.ebi.ac.uk/pdbsum/4ibi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibi ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:56, 9 November 2022

2022-11-09T08:56:32Z

← Older revision		Revision as of 08:56, 9 November 2022
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	<StructureSection load='4ibi' size='340' side='right'caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='4ibi' size='340' side='right'caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Ebov~~-~~may Ebov~~-~~may~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4IBI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Mayinga,_Zaire,_1976 Ebola virus - Mayinga, Zaire, 1976]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IBI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [https://pdbe.org/4ibi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [https://www.ebi.ac.uk/pdbsum/4ibi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibi ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOV-May])~~</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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [~~http~~://pdbe.org/4ibi PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ibi PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibi ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>		[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Ebov~~-~~may~~]]		[[Category: Ebola virus - Mayinga, Zaire, 1976]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Amarasinghe~~, G K~~]]		[[Category: Amarasinghe GK]]
	[[Category: Binning~~, J M~~]]		[[Category: Binning JM]]
	[[Category: Borek~~, D M~~]]		[[Category: Borek DM]]
	[[Category: Brown~~, C S~~]]		[[Category: Brown CS]]
	[[Category: Leung~~, D W~~]]		[[Category: Leung DW]]
	[[Category: Otwinowski, Z]]		[[Category: Otwinowski Z]]
	[[Category: Peterson~~, D S~~]]		[[Category: Peterson DS]]
	[[Category: Ramanan, P]]		[[Category: Ramanan P]]
	[[Category: Stubbs~~, A J~~]]		[[Category: Stubbs AJ]]
	[[Category: Xu, W]]		[[Category: Xu W]]
	~~[[Category: Interferon inhibitor domain]]~~
	~~[[Category: Transcription-transcription inhibitor complex~~]]

OCA at 11:59, 17 July 2019

2019-07-17T11:59:59Z

← Older revision		Revision as of 11:59, 17 July 2019
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	==Ebola virus VP35 bound to small molecule==		==Ebola virus VP35 bound to small molecule==
	<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='4ibi' size='340' side='right'caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebov-may Ebov-may]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IBI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebov-may Ebov-may]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IBI FirstGlance]. <br>
Line 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Ebov-may]]		[[Category: Ebov-may]]
			[[Category: Large Structures]]
	[[Category: Amarasinghe, G K]]		[[Category: Amarasinghe, G K]]
	[[Category: Binning, J M]]		[[Category: Binning, J M]]

OCA at 08:52, 15 November 2017

2017-11-15T08:52:28Z

← Older revision		Revision as of 08:52, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Ebozm Ebozm~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IBI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebov-may Ebov-may]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IBI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 ~~EBOZM~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOV-May])</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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [http://pdbe.org/4ibi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [http://www.ebi.ac.uk/pdbsum/4ibi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibi ProSAT]</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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [http://pdbe.org/4ibi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [http://www.ebi.ac.uk/pdbsum/4ibi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibi ProSAT]</span></td></tr>
	</table>		</table>
Line 24:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Ebozm~~]]		[[Category: Ebov-may]]
	[[Category: Amarasinghe, G K]]		[[Category: Amarasinghe, G K]]
	[[Category: Binning, J M]]		[[Category: Binning, J M]]

OCA at 21:03, 5 August 2016

2016-08-05T21:03:15Z

← Older revision		Revision as of 21:03, 5 August 2016
Line 1:		Line 1:

	==Ebola virus VP35 bound to small molecule==		==Ebola virus VP35 bound to small molecule==
	<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOZM])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOZM])</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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [http://www.ebi.ac.uk/pdbsum/4ibi 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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [http://pdbe.org/4ibi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [http://www.ebi.ac.uk/pdbsum/4ibi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibi ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4ibi" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:53, 25 December 2014

2014-12-25T21:53:06Z

← Older revision		Revision as of 21:53, 25 December 2014
Line 2:		Line 2:
	<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>		<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebozm Ebozm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. <br>		<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebozm Ebozm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IBI FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOZM])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOZM])</td></tr>
	<tr~~><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class~~='~~plainlinks~~'~~>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [http://www.ebi.ac.uk/pdbsum/4ibi PDBsum]</span></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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [http://www.ebi.ac.uk/pdbsum/4ibi PDBsum]</span></td></tr>		</table>
	<table>		== Function ==
			[[http://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 15:		Line 16:
	In Silico Derived Small Molecules Bind the Filovirus VP35 Protein and Inhibit Its Polymerase Cofactor Activity.,Brown CS, Lee MS, Leung DW, Wang T, Xu W, Luthra P, Anantpadma M, Shabman RS, Melito LM, Macmillan KS, Borek DM, Otwinowski Z, Ramanan P, Stubbs AJ, Peterson DS, Binning JM, Tonelli M, Olson MA, Davey R, Ready JM, Basler CF, Amarasinghe GK J Mol Biol. 2014 Feb 1. pii: S0022-2836(14)00048-5. doi:, 10.1016/j.jmb.2014.01.010. PMID:24495995<ref>PMID:24495995</ref>		In Silico Derived Small Molecules Bind the Filovirus VP35 Protein and Inhibit Its Polymerase Cofactor Activity.,Brown CS, Lee MS, Leung DW, Wang T, Xu W, Luthra P, Anantpadma M, Shabman RS, Melito LM, Macmillan KS, Borek DM, Otwinowski Z, Ramanan P, Stubbs AJ, Peterson DS, Binning JM, Tonelli M, Olson MA, Davey R, Ready JM, Basler CF, Amarasinghe GK J Mol Biol. 2014 Feb 1. pii: S0022-2836(14)00048-5. doi:, 10.1016/j.jmb.2014.01.010. PMID:24495995<ref>PMID:24495995</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 22:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Ebozm]]		[[Category: Ebozm]]
	[[Category: Amarasinghe, G K.]]		[[Category: Amarasinghe, G K]]
	[[Category: Binning, J M.]]		[[Category: Binning, J M]]
	[[Category: Borek, D M.]]		[[Category: Borek, D M]]
	[[Category: Brown, C S.]]		[[Category: Brown, C S]]
	[[Category: Leung, D W.]]		[[Category: Leung, D W]]
	[[Category: Otwinowski, Z.]]		[[Category: Otwinowski, Z]]
	[[Category: Peterson, D S.]]		[[Category: Peterson, D S]]
	[[Category: Ramanan, P.]]		[[Category: Ramanan, P]]
	[[Category: Stubbs, A J.]]		[[Category: Stubbs, A J]]
	[[Category: Xu, W.]]		[[Category: Xu, W]]
	[[Category: Interferon inhibitor domain]]		[[Category: Interferon inhibitor domain]]
	[[Category: Transcription-transcription inhibitor complex]]		[[Category: Transcription-transcription inhibitor complex]]

OCA at 06:47, 14 May 2014

2014-05-14T06:47:12Z

← Older revision		Revision as of 06:47, 14 May 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4ibi~~\| ~~PDB~~=4ibi \| ~~SCENE~~= }}		==Ebola virus VP35 bound to small molecule==
	===Ebola virus VP35 ~~bound~~ to small ~~molecule===~~		<StructureSection load='4ibi' size='340' side='right' caption='[[4ibi]], [[Resolution\|resolution]] 1.47Å' scene=''>
	~~{{ABSTRACT_PUBMED_24495995}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4ibi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebozm Ebozm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1D8:3-{(2S)-2-(7-CHLORO-1,3-BENZODIOXOL-5-YL)-4-HYDROXY-5-OXO-3-[3-(TRIFLUOROMETHYL)BENZOYL]-2,5-DIHYDRO-1H-PYRROL-1-YL}BENZOIC+ACID'>1D8</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ibb\|4ibb]], [[4ibc\|4ibc]], [[4ibd\|4ibd]], [[4ibe\|4ibe]], [[4ibf\|4ibf]], [[4ibh\|4ibh]], [[4ibj\|4ibj]], [[4ibk\|4ibk]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOZM])</td></tr>
			<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></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=4ibi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ibi RCSB], [http://www.ebi.ac.uk/pdbsum/4ibi PDBsum]</span></td></tr>
			<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The Ebola virus (EBOV) genome only encodes a single viral polypeptide with enzymatic activity, the viral large (L) RNA-dependent RNA polymerase protein. However, currently, there is limited information about the L protein, which has hampered the development of antivirals. Therefore, antifiloviral therapeutic efforts must include additional targets such as protein-protein interfaces. Viral protein 35 (VP35) is multifunctional and plays important roles in viral pathogenesis, including viral mRNA synthesis and replication of the negative-sense RNA viral genome. Previous studies revealed that mutation of key basic residues within the VP35 interferon inhibitory domain (IID) results in significant EBOV attenuation, both in vitro and in vivo. In the current study, we use an experimental pipeline that includes structure-based in silico screening and biochemical and structural characterization, along with medicinal chemistry, to identify and characterize small molecules that target a binding pocket within VP35. NMR mapping experiments and high-resolution x-ray crystal structures show that select small molecules bind to a region of VP35 IID that is important for replication complex formation through interactions with the viral nucleoprotein (NP). We also tested select compounds for their ability to inhibit VP35 IID-NP interactions in vitro as well as VP35 function in a minigenome assay and EBOV replication. These results confirm the ability of compounds identified in this study to inhibit VP35-NP interactions in vitro and to impair viral replication in cell-based assays. These studies provide an initial framework to guide development of antifiloviral compounds against filoviral VP35 proteins.

	~~==Function==~~		In Silico Derived Small Molecules Bind the Filovirus VP35 Protein and Inhibit Its Polymerase Cofactor Activity.,Brown CS, Lee MS, Leung DW, Wang T, Xu W, Luthra P, Anantpadma M, Shabman RS, Melito LM, Macmillan KS, Borek DM, Otwinowski Z, Ramanan P, Stubbs AJ, Peterson DS, Binning JM, Tonelli M, Olson MA, Davey R, Ready JM, Basler CF, Amarasinghe GK J Mol Biol. 2014 Feb 1. pii: S0022-2836(14)00048-5. doi:, 10.1016/j.jmb.2014.01.010. PMID:24495995<ref>PMID:24495995</ref>
	~~[[http://www~~.~~uniprot~~.~~org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex~~. ~~Prevents establishment of cellular antiviral state by blocking virus~~-~~induced phosphorylation and activation of interferon regulatory factor 3~~ (~~IRF3~~)~~, a transcription factor critical for the induction of interferons alpha and beta~~. ~~The mechanism by which this blockage occurs remains incompletely defined~~, ~~a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA~~. ~~Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2~~/~~PKR~~.~~<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>~~PMID:~~12829834</ref> <ref>PMID:16495261</ref>~~ <ref>PMID:~~17065211~~</ref>

	~~==About this Structure==~~		From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
	~~[[4ibi]] is~~ a ~~2 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4IBI OCA].~~		</div>
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:024495995</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
			[[Category: Ebozm]]
	[[Category: Amarasinghe, G K.]]		[[Category: Amarasinghe, G K.]]
	[[Category: Binning, J M.]]		[[Category: Binning, J M.]]

OCA at 08:52, 19 March 2014

2014-03-19T08:52:01Z

← Older revision		Revision as of 08:52, 19 March 2014
Line 1:		Line 1:
	~~WITHDRAWN~~: The ~~PDB entry~~ 4IBI ~~was withdrawn~~.		{{STRUCTURE_4ibi\| PDB=4ibi \| SCENE= }}
			===Ebola virus VP35 bound to small molecule===
			{{ABSTRACT_PUBMED_24495995}}

			==Function==
			[[http://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>

			==About this Structure==
			[[4ibi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBI OCA].

			==Reference==
			<ref group="xtra">PMID:024495995</ref><references group="xtra"/><references/>
			[[Category: Amarasinghe, G K.]]
			[[Category: Binning, J M.]]
			[[Category: Borek, D M.]]
			[[Category: Brown, C S.]]
			[[Category: Leung, D W.]]
			[[Category: Otwinowski, Z.]]
			[[Category: Peterson, D S.]]
			[[Category: Ramanan, P.]]
			[[Category: Stubbs, A J.]]
			[[Category: Xu, W.]]
			[[Category: Interferon inhibitor domain]]
			[[Category: Transcription-transcription inhibitor complex]]

OCA at 09:55, 18 December 2013

2013-12-18T09:55:35Z

← Older revision		Revision as of 09:55, 18 December 2013
Line 1:		Line 1:
	~~'''Unreleased structure'''~~		WITHDRAWN: The PDB entry 4IBI was withdrawn.

	The entry ~~4ibi is ON HOLD until Paper Publication~~

	~~Authors: Brown, C.S., Leung, D.W., Xu, W~~.~~, Borek, D.M., Otwinowski, Z., Ramanan, P., Stubbs, A.J., Peterson, D.S., Binning, J.M., Amarasinghe, G.K.~~

	~~Description: ebolavirus virus VP35 protein and its inhibitor VPL57 complex~~

OCA at 13:23, 20 February 2013

2013-02-20T13:23:31Z

← Older revision		Revision as of 13:23, 20 February 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4ibi is ON HOLD		The entry 4ibi is ON HOLD until Paper Publication

	Authors: Brown, C.S., Leung, D.W., Xu, W., Borek, D.M., Otwinowski, Z., Ramanan, P., Stubbs, A.J., Peterson, D.S., Binning, J.M., Amarasinghe, G.K.		Authors: Brown, C.S., Leung, D.W., Xu, W., Borek, D.M., Otwinowski, Z., Ramanan, P., Stubbs, A.J., Peterson, D.S., Binning, J.M., Amarasinghe, G.K.

	Description: ebolavirus virus VP35 protein and its inhibitor VPL57 complex		Description: ebolavirus virus VP35 protein and its inhibitor VPL57 complex