4e5f - Revision history

OCA at 14:52, 14 March 2024

2024-03-14T14:52:59Z

← Older revision		Revision as of 14:52, 14 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E5F FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E5F FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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]] 2.392Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [https://pdbe.org/4e5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [https://www.ebi.ac.uk/pdbsum/4e5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5f 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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [https://pdbe.org/4e5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [https://www.ebi.ac.uk/pdbsum/4e5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5f 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 4e5f" 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

2022-09-28T06:51:04Z

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

	==Crystal structure of avian influenza virus PAn bound to compound 1==		==Crystal structure of avian influenza virus PAn bound to compound 1==
	<StructureSection load='4e5f' size='340' side='right' caption='[[4e5f]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='4e5f' size='340' side='right'caption='[[4e5f]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E5F FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E5F FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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]], [[4e5g\|4e5g]], [[4e5h\|4e5h]], [[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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [https://pdbe.org/4e5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [https://www.ebi.ac.uk/pdbsum/4e5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5f 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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [~~http~~://pdbe.org/4e5f PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e5f PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5f 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 4e5f" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e5f" 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

2017-11-16T05:28:01Z

← Older revision		Revision as of 05:28, 16 November 2017
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4e5f" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e5f" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:59, 4 August 2016

2016-08-04T17:59:48Z

← Older revision		Revision as of 17:59, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of avian influenza virus PAn bound to compound 1==		==Crystal structure of avian influenza virus PAn bound to compound 1==
	<StructureSection load='4e5f' size='340' side='right' caption='[[4e5f]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='4e5f' size='340' side='right' caption='[[4e5f]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5F FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5F FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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]], [[4e5g\|4e5g]], [[4e5h\|4e5h]], [[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]], [[4e5g\|4e5g]], [[4e5h\|4e5h]], [[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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [http://www.ebi.ac.uk/pdbsum/4e5f 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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [http://pdbe.org/4e5f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [http://www.ebi.ac.uk/pdbsum/4e5f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e5f 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 4e5f" 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 11:40, 25 December 2014

2014-12-25T11:40:54Z

← Older revision		Revision as of 11:40, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5F FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5F FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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]], [[4e5g\|4e5g]], [[4e5h\|4e5h]], [[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]], [[4e5g\|4e5g]], [[4e5h\|4e5h]], [[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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [http://www.ebi.ac.uk/pdbsum/4e5f 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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [http://www.ebi.ac.uk/pdbsum/4e5f 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 09:10, 11 June 2014

2014-06-11T09:10:12Z

← Older revision		Revision as of 09:10, 11 June 2014
Line 1:		Line 1:
	[[~~Image~~:~~4e5f~~.~~png~~\|~~left~~\|~~200px~~]]		==Crystal structure of avian influenza virus PAn bound to compound 1==
			<StructureSection load='4e5f' size='340' side='right' caption='[[4e5f]], [[Resolution\|resolution]] 2.39Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4e5f]] 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=4E5F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E5F FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0N7:2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONE'>0N7</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]], [[4e5g\|4e5g]], [[4e5h\|4e5h]], [[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=4e5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e5f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e5f RCSB], [http://www.ebi.ac.uk/pdbsum/4e5f 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_4e5f\| PDB=4e5f \| 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 1===~~		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 ==
	[[~~4e5f]] 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=4E5F 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 05:07, 22 August 2012

2012-08-22T05:07:49Z

← Older revision		Revision as of 05:07, 22 August 2012
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	[[Image:4e5f.~~jpg~~\|left\|200px]]		[[Image:4e5f.png\|left\|200px]]

	{{STRUCTURE_4e5f\| PDB=4e5f \| SCENE= }}		{{STRUCTURE_4e5f\| PDB=4e5f \| SCENE= }}
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	===Crystal structure of avian influenza virus PAn bound to compound 1===		===Crystal structure of avian influenza virus PAn bound to compound 1===

			{{ABSTRACT_PUBMED_22876176}}

	==About this Structure==		==About this Structure==
	[[4e5f]] 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=4E5F OCA].		[[4e5f]] 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=4E5F 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

2012-08-08T05:33:13Z

← Older revision		Revision as of 05:33, 8 August 2012
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	~~'''Unreleased structure'''~~		[[Image:4e5f.jpg\|left\|200px]]

	~~The entry~~ 4e5f ~~is ON HOLD~~ ~~until Paper Publication~~		{{STRUCTURE_4e5f\| PDB=4e5f \| SCENE= }}

	~~Authors: DuBois, R.M., Slavish, P.J., Webb, T.R., White, S.W.~~		===Crystal structure of avian influenza virus PAn bound to compound 1===

	~~Description~~: ~~Crystal structure of avian influenza~~ virus ~~PAn bound to compound 1~~
			==About this Structure==
			[[4e5f]] 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=4E5F 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 07:22, 28 March 2012

2012-03-28T07:22:14Z

← Older revision		Revision as of 07:22, 28 March 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4e5f is ON HOLD		The entry 4e5f 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 1		Description: Crystal structure of avian influenza virus PAn bound to compound 1

OCA: Protected "4e5f" [edit=sysop:move=sysop]

2012-03-21T07:17:53Z

Protected "4e5f" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:17, 21 March 2012
(No difference)