4e5h - Revision history

OCA at 14:53, 14 March 2024

OCA — Thu, 14 Mar 2024 14:53:06 GMT

←Older revision		Revision as of 14:53, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Viet_Nam/1203/2004(H5N1)) Influenza A virus (A/Viet Nam/1203/2004(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E5H FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Viet_Nam/1203/2004(H5N1)) Influenza A virus (A/Viet Nam/1203/2004(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E5H FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.158Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [https://pdbe.org/4e5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [https://www.ebi.ac.uk/pdbsum/4e5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5h 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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [https://pdbe.org/4e5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [https://www.ebi.ac.uk/pdbsum/4e5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5h ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/Q5EP34_9INFA Q5EP34_9INFA]]	+	[https://www.uniprot.org/uniprot/Q5EP34_9INFA Q5EP34_9INFA]
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Emerging influenza viruses are a serious threat to human health because of their pandemic potential. A promising target for the development of novel anti-influenza therapeutics is the PA protein, whose endonuclease activity is essential for viral replication. Translation of viral mRNAs by the host ribosome requires mRNA capping for recognition and binding, and the necessary mRNA caps are cleaved or "snatched" from host pre-mRNAs by the PA endonuclease. The structure-based development of inhibitors that target PA endonuclease is now possible with the recent crystal structure of the PA catalytic domain. In this study, we sought to understand the molecular mechanism of inhibition by several compounds that are known or predicted to block endonuclease-dependent polymerase activity. Using an in vitro endonuclease activity assay, we show that these compounds block the enzymatic activity of the isolated PA endonuclease domain. Using X-ray crystallography, we show how these inhibitors coordinate the two-metal endonuclease active site and engage the active site residues. Two structures also reveal an induced-fit mode of inhibitor binding. The structures allow a molecular understanding of the structure-activity relationship of several known influenza inhibitors and the mechanism of drug resistance by a PA mutation. Taken together, our data reveal new strategies for structure-based design and optimization of PA endonuclease inhibitors.	+
-		+
-	Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the PA Endonuclease.,Dubois RM, Slavish PJ, Baughman BM, Yun MK, Bao J, Webby RJ, Webb TR, White SW PLoS Pathog. 2012 Aug;8(8):e1002830. Epub 2012 Aug 2. PMID:22876176<ref>PMID:22876176</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4e5h" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]		*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:51, 28 September 2022

OCA — Wed, 28 Sep 2022 06:51:11 GMT

←Older revision		Revision as of 06:51, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of avian influenza virus PAn bound to compound 3==		==Crystal structure of avian influenza virus PAn bound to compound 3==
-	<StructureSection load='4e5h' size='340' side='right' caption='[[4e5h]], [[Resolution\|resolution]] 2.16Å' scene=''>	+	<StructureSection load='4e5h' size='340' side='right'caption='[[4e5h]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Influenza_a_virus_~~(a/~~viet_nam~~/1203/2004(~~h5n1~~)) Influenza a virus (a/~~viet nam~~/1203/2004(~~h5n1~~))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E5H FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Viet_Nam/1203/2004(H5N1)) Influenza A virus (A/Viet Nam/1203/2004(H5N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E5H FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e5e\|4e5e]], [[4e5f\|4e5f]], [[4e5g\|4e5g]], [[4e5i\|4e5i]], [[4e5j\|4e5j]], [[4e5l\|4e5l]]</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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [https://pdbe.org/4e5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [https://www.ebi.ac.uk/pdbsum/4e5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5h ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284218 Influenza A virus (A/Viet Nam/1203/2004(H5N1))])</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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [~~http~~://pdbe.org/4e5h PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e5h PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5h ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/Q5EP34_9INFA Q5EP34_9INFA]]
	<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 4e5h" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e5h" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~DuBois, R M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Slavish, P J~~]]	+	[[Category: DuBois RM]]
-	[[Category: ~~Webb, T R~~]]	+	[[Category: Slavish PJ]]
-	[[Category: ~~White, S W~~]]	+	[[Category: Webb TR]]
-	[[Category: ~~Endonuclease domain]]~~	+	[[Category: White SW]]
-	~~[[Category: H5n1 subtype]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 05:28, 16 November 2017

OCA — Thu, 16 Nov 2017 05:28:18 GMT

←Older revision		Revision as of 05:28, 16 November 2017
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4e5h" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e5h" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:56, 5 August 2016

OCA — Fri, 05 Aug 2016 13:56:40 GMT

←Older revision		Revision as of 13:56, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of avian influenza virus PAn bound to compound 3==		==Crystal structure of avian influenza virus PAn bound to compound 3==
	<StructureSection load='4e5h' size='340' side='right' caption='[[4e5h]], [[Resolution\|resolution]] 2.16Å' scene=''>		<StructureSection load='4e5h' size='340' side='right' caption='[[4e5h]], [[Resolution\|resolution]] 2.16Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Influenza_a_virus~~ Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5H FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/viet_nam/1203/2004(h5n1)) Influenza a virus (a/viet nam/1203/2004(h5n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5H FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e5e\|4e5e]], [[4e5f\|4e5f]], [[4e5g\|4e5g]], [[4e5i\|4e5i]], [[4e5j\|4e5j]], [[4e5l\|4e5l]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e5e\|4e5e]], [[4e5f\|4e5f]], [[4e5g\|4e5g]], [[4e5i\|4e5i]], [[4e5j\|4e5j]], [[4e5l\|4e5l]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~11320~~ Influenza A virus])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=284218 Influenza A virus (A/Viet Nam/1203/2004(H5N1))])</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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [http://www.ebi.ac.uk/pdbsum/4e5h 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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [http://pdbe.org/4e5h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [http://www.ebi.ac.uk/pdbsum/4e5h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5h 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 4e5h" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 23:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Influenza a virus]]
	[[Category: DuBois, R M]]		[[Category: DuBois, R M]]
	[[Category: Slavish, P J]]		[[Category: Slavish, P J]]

OCA at 19:22, 25 December 2014

OCA — Thu, 25 Dec 2014 19:22:17 GMT

←Older revision		Revision as of 19:22, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5H FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5H FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e5e\|4e5e]], [[4e5f\|4e5f]], [[4e5g\|4e5g]], [[4e5i\|4e5i]], [[4e5j\|4e5j]], [[4e5l\|4e5l]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e5e\|4e5e]], [[4e5f\|4e5f]], [[4e5g\|4e5g]], [[4e5i\|4e5i]], [[4e5j\|4e5j]], [[4e5l\|4e5l]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11320 Influenza A virus])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11320 Influenza A virus])</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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [http://www.ebi.ac.uk/pdbsum/4e5h 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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [http://www.ebi.ac.uk/pdbsum/4e5h 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 24:		Line 24:
	</StructureSection>		</StructureSection>
	[[Category: Influenza a virus]]		[[Category: Influenza a virus]]
-	[[Category: DuBois, R M.]]	+	[[Category: DuBois, R M]]
-	[[Category: Slavish, P J.]]	+	[[Category: Slavish, P J]]
-	[[Category: Webb, T R.]]	+	[[Category: Webb, T R]]
-	[[Category: White, S W.]]	+	[[Category: White, S W]]
	[[Category: Endonuclease domain]]		[[Category: Endonuclease domain]]
	[[Category: H5n1 subtype]]		[[Category: H5n1 subtype]]
	[[Category: Transcription]]		[[Category: Transcription]]
	[[Category: Viral protein]]		[[Category: Viral protein]]

OCA at 09:18, 11 June 2014

OCA — Wed, 11 Jun 2014 09:18:06 GMT

←Older revision		Revision as of 09:18, 11 June 2014
Line 1:		Line 1:
-	[[~~Image:~~4e5h.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of avian influenza virus PAn bound to compound 3==
		+	<StructureSection load='4e5h' size='340' side='right' caption='[[4e5h]], [[Resolution\|resolution]] 2.16Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5H FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N8:(2Z)-4-[1-BENZYL-4-(4-CHLOROBENZYL)PIPERIDIN-4-YL]-2-HYDROXY-4-OXOBUT-2-ENOIC+ACID'>0N8</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4e5e\|4e5e]], [[4e5f\|4e5f]], [[4e5g\|4e5g]], [[4e5i\|4e5i]], [[4e5j\|4e5j]], [[4e5l\|4e5l]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11320 Influenza A virus])</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=4e5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5h RCSB], [http://www.ebi.ac.uk/pdbsum/4e5h PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Emerging influenza viruses are a serious threat to human health because of their pandemic potential. A promising target for the development of novel anti-influenza therapeutics is the PA protein, whose endonuclease activity is essential for viral replication. Translation of viral mRNAs by the host ribosome requires mRNA capping for recognition and binding, and the necessary mRNA caps are cleaved or "snatched" from host pre-mRNAs by the PA endonuclease. The structure-based development of inhibitors that target PA endonuclease is now possible with the recent crystal structure of the PA catalytic domain. In this study, we sought to understand the molecular mechanism of inhibition by several compounds that are known or predicted to block endonuclease-dependent polymerase activity. Using an in vitro endonuclease activity assay, we show that these compounds block the enzymatic activity of the isolated PA endonuclease domain. Using X-ray crystallography, we show how these inhibitors coordinate the two-metal endonuclease active site and engage the active site residues. Two structures also reveal an induced-fit mode of inhibitor binding. The structures allow a molecular understanding of the structure-activity relationship of several known influenza inhibitors and the mechanism of drug resistance by a PA mutation. Taken together, our data reveal new strategies for structure-based design and optimization of PA endonuclease inhibitors.

-	~~{{STRUCTURE_4e5h\| PDB=4e5h \| SCENE= }}~~	+	Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the PA Endonuclease.,Dubois RM, Slavish PJ, Baughman BM, Yun MK, Bao J, Webby RJ, Webb TR, White SW PLoS Pathog. 2012 Aug;8(8):e1002830. Epub 2012 Aug 2. PMID:22876176<ref>PMID:22876176</ref>

-	~~===Crystal structure~~ of ~~avian influenza virus PAn bound to compound 3===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22876176}}~~	+	==See Also==
-		+	*[[RNA polymerase\|RNA polymerase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4e5h~~]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:022876176<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Influenza a virus]]		[[Category: Influenza a virus]]
	[[Category: DuBois, R M.]]		[[Category: DuBois, R M.]]

OCA at 05:02, 22 August 2012

OCA — Wed, 22 Aug 2012 05:02:51 GMT

←Older revision		Revision as of 05:02, 22 August 2012
Line 1:		Line 1:
-	[[Image:4e5h.~~jpg~~\|left\|200px]]	+	[[Image:4e5h.png\|left\|200px]]

	{{STRUCTURE_4e5h\| PDB=4e5h \| SCENE= }}		{{STRUCTURE_4e5h\| PDB=4e5h \| SCENE= }}
Line 5:		Line 5:
	===Crystal structure of avian influenza virus PAn bound to compound 3===		===Crystal structure of avian influenza virus PAn bound to compound 3===

		+	{{ABSTRACT_PUBMED_22876176}}

	==About this Structure==		==About this Structure==
	[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA].		[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022876176</ref><references group="xtra"/>
	[[Category: Influenza a virus]]		[[Category: Influenza a virus]]
	[[Category: DuBois, R M.]]		[[Category: DuBois, R M.]]

OCA at 05:33, 8 August 2012

OCA — Wed, 08 Aug 2012 05:33:12 GMT

←Older revision		Revision as of 05:33, 8 August 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4e5h.jpg\|left\|200px]]

-	~~The entry~~ 4e5h ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4e5h\| PDB=4e5h \| SCENE= }}

-	~~Authors: DuBois, R.M., Slavish, P.J., Webb, T.R., White, S.W.~~	+	===Crystal structure of avian influenza virus PAn bound to compound 3===

-	~~Description: Crystal~~ structure ~~of avian influenza~~ virus ~~PAn bound to compound 3~~	+
		+	==About this Structure==
		+	[[4e5h]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E5H OCA].
		+	[[Category: Influenza a virus]]
		+	[[Category: DuBois, R M.]]
		+	[[Category: Slavish, P J.]]
		+	[[Category: Webb, T R.]]
		+	[[Category: White, S W.]]
		+	[[Category: Endonuclease domain]]
		+	[[Category: H5n1 subtype]]
		+	[[Category: Transcription]]
		+	[[Category: Viral protein]]

OCA at 06:38, 11 April 2012

OCA — Wed, 11 Apr 2012 06:38:55 GMT

←Older revision		Revision as of 06:38, 11 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4e5h is ON HOLD	+	The entry 4e5h is ON HOLD until Paper Publication

	Authors: DuBois, R.M., Slavish, P.J., Webb, T.R., White, S.W.		Authors: DuBois, R.M., Slavish, P.J., Webb, T.R., White, S.W.

	Description: Crystal structure of avian influenza virus PAn bound to compound 3		Description: Crystal structure of avian influenza virus PAn bound to compound 3

OCA: Protected "4e5h" [edit=sysop:move=sysop]

OCA — Wed, 21 Mar 2012 07:17:56 GMT

Protected "4e5h" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:17, 21 March 2012