5wa6 - Revision history

OCA at 14:14, 13 March 2024

OCA — Wed, 13 Mar 2024 14:14:54 GMT

←Older revision		Revision as of 14:14, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='5wa6' size='340' side='right'caption='[[5wa6]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='5wa6' size='340' side='right'caption='[[5wa6]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wa6]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~I09a0 I09a0~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WA6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wa6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/California/04/2009(H1N1)) Influenza A virus (A/California/04/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WA6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KU7:2-{(2S)-1-[(2-fluorophenoxy)acetyl]pyrrolidin-2-yl}-5-hydroxy-6-oxo-N-(2-phenoxyethyl)-1,6-dihydropyrimidine-4-carboxamide'>KU7</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5w3i\|5w3i]], [[5w44\|5w44]], [[5w73\|5w73]], [[5w7u\|5w7u]], [[5w92\|5w92]], [[5w9g\|5w9g]], [[5wa7\|5wa7]], [[5wb3\|5wb3]], [[5wap\|5wap]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KU7:2-{(2S)-1-[(2-fluorophenoxy)acetyl]pyrrolidin-2-yl}-5-hydroxy-6-oxo-N-(2-phenoxyethyl)-1,6-dihydropyrimidine-4-carboxamide'>KU7</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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=641501 I09A0])~~</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=5wa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa6 OCA], [https://pdbe.org/5wa6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wa6 RCSB], [https://www.ebi.ac.uk/pdbsum/5wa6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa6 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=5wa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa6 OCA], [~~http~~://pdbe.org/5wa6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wa6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wa6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa6 ProSAT]</span></td></tr>	+
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/C3W5S0_I09A0 C3W5S0_I09A0]
-	Influenza is a serious hazard to human health that causes hundreds of thousands of deaths annually. Though vaccines and current therapeutics can blunt some of the perilous impact of this viral infection, new treatments are needed due to the constantly evolving nature of this virus. Recently, our growing understanding of an essential influenza viral protein, PA, has led to the development of focused libraries of new small molecules that specifically target the active site of the PA influenza endonuclease, which we report here. Our overarching approach has been to proactively develop lead inhibitors that are less likely to rapidly develop clinical resistance by optimizing inhibitors that retain activity against induced resistant mutants. Here, we report details behind the discovery of new potent inhibitors of wild type and resistant mutant endonucleases along with their high-resolution co-crystal structure-activity relationships. These results add to our understanding of nuclease protein targets and potentially serve as starting points for a new therapeutic approach to the treatment of influenza.	+
-		+
-	Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease.,Beylkin D, Kumar G, Zhou W, Park J, Jeevan T, Lagisetti C, Harfoot R, Webby RJ, White SW, Webb TR Sci Rep. 2017 Dec 7;7(1):~~17139. doi: 10.1038~~/~~s41598-017-17419-6. PMID:29215062<ref>PMID:29215062<~~/~~ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U~~.S. ~~National Library of Medicine.<br>~~	+
-	</~~div>~~	+
-	~~<div class="pdbe-citations 5wa6" style="background-color:#fffaf0;"><~~/~~div>~~	+

	==See Also==		==See Also==
-	*[[RNA polymerase\|RNA polymerase]]	+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: I09a0]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kumar, G]]	+	[[Category: Kumar G]]
-	[[Category: White~~, S W]]~~	+	[[Category: White SW]]
-	~~[[Category: Cap-snatching]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Nuclease]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Virus~~]]	+

OCA at 07:23, 23 May 2019

OCA — Thu, 23 May 2019 07:23:09 GMT

←Older revision		Revision as of 07:23, 23 May 2019
Line 1:		Line 1:

	==Crystal structure of the influenza virus PA endonuclease in complex with an inhibitor - SRI-30007==		==Crystal structure of the influenza virus PA endonuclease in complex with an inhibitor - SRI-30007==
-	<StructureSection load='5wa6' size='340' side='right' caption='[[5wa6]], [[Resolution\|resolution]] 2.25Å' scene=''>	+	<StructureSection load='5wa6' size='340' side='right'caption='[[5wa6]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wa6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WA6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wa6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/I09a0 I09a0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WA6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KU7:2-{(2S)-1-[(2-fluorophenoxy)acetyl]pyrrolidin-2-yl}-5-hydroxy-6-oxo-N-(2-phenoxyethyl)-1,6-dihydropyrimidine-4-carboxamide'>KU7</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KU7:2-{(2S)-1-[(2-fluorophenoxy)acetyl]pyrrolidin-2-yl}-5-hydroxy-6-oxo-N-(2-phenoxyethyl)-1,6-dihydropyrimidine-4-carboxamide'>KU7</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5w3i\|5w3i]], [[5w44\|5w44]], [[5w73\|5w73]], [[5w7u\|5w7u]], [[5w92\|5w92]], [[5w9g\|5w9g]], [[5wa7\|5wa7]], [[5wb3\|5wb3]], [[5wap\|5wap]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5w3i\|5w3i]], [[5w44\|5w44]], [[5w73\|5w73]], [[5w7u\|5w7u]], [[5w92\|5w92]], [[5w9g\|5w9g]], [[5wa7\|5wa7]], [[5wb3\|5wb3]], [[5wap\|5wap]]</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=641501 I09A0])</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=5wa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa6 OCA], [http://pdbe.org/5wa6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wa6 RCSB], [http://www.ebi.ac.uk/pdbsum/5wa6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa6 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=5wa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa6 OCA], [http://pdbe.org/5wa6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wa6 RCSB], [http://www.ebi.ac.uk/pdbsum/5wa6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa6 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Influenza is a serious hazard to human health that causes hundreds of thousands of deaths annually. Though vaccines and current therapeutics can blunt some of the perilous impact of this viral infection, new treatments are needed due to the constantly evolving nature of this virus. Recently, our growing understanding of an essential influenza viral protein, PA, has led to the development of focused libraries of new small molecules that specifically target the active site of the PA influenza endonuclease, which we report here. Our overarching approach has been to proactively develop lead inhibitors that are less likely to rapidly develop clinical resistance by optimizing inhibitors that retain activity against induced resistant mutants. Here, we report details behind the discovery of new potent inhibitors of wild type and resistant mutant endonucleases along with their high-resolution co-crystal structure-activity relationships. These results add to our understanding of nuclease protein targets and potentially serve as starting points for a new therapeutic approach to the treatment of influenza.
		+
		+	Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease.,Beylkin D, Kumar G, Zhou W, Park J, Jeevan T, Lagisetti C, Harfoot R, Webby RJ, White SW, Webb TR Sci Rep. 2017 Dec 7;7(1):17139. doi: 10.1038/s41598-017-17419-6. PMID:29215062<ref>PMID:29215062</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5wa6" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase\|RNA polymerase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: I09a0]]
		+	[[Category: Large Structures]]
	[[Category: Kumar, G]]		[[Category: Kumar, G]]
	[[Category: White, S W]]		[[Category: White, S W]]

OCA at 07:59, 2 May 2018

OCA — Wed, 02 May 2018 07:59:26 GMT

←Older revision		Revision as of 07:59, 2 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5wa6 is ON HOLD until Paper Publication~~	+	==Crystal structure of the influenza virus PA endonuclease in complex with an inhibitor - SRI-30007==
-		+	<StructureSection load='5wa6' size='340' side='right' caption='[[5wa6]], [[Resolution\|resolution]] 2.25Å' scene=''>
-	~~Authors: Kumar, G., White, S.W.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5wa6]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WA6 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of the influenza virus PA endonuclease in complex with an inhibitor -SRI-30007	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KU7:2-{(2S)-1-[(2-fluorophenoxy)acetyl]pyrrolidin-2-yl}-5-hydroxy-6-oxo-N-(2-phenoxyethyl)-1,6-dihydropyrimidine-4-carboxamide'>KU7</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5w3i\|5w3i]], [[5w44\|5w44]], [[5w73\|5w73]], [[5w7u\|5w7u]], [[5w92\|5w92]], [[5w9g\|5w9g]], [[5wa7\|5wa7]], [[5wb3\|5wb3]], [[5wap\|5wap]]</td></tr>
-	[[~~Category~~: ~~White~~, S.W]]	+	<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=5wa6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa6 OCA], [http://pdbe.org/5wa6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wa6 RCSB], [http://www.ebi.ac.uk/pdbsum/5wa6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa6 ProSAT]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
	[[Category: Kumar, G]]		[[Category: Kumar, G]]
		+	[[Category: White, S W]]
		+	[[Category: Cap-snatching]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Nuclease]]
		+	[[Category: Transcription]]
		+	[[Category: Virus]]

OCA at 04:36, 31 January 2018

OCA — Wed, 31 Jan 2018 04:36:11 GMT

←Older revision		Revision as of 04:36, 31 January 2018
Line 3:		Line 3:
	The entry 5wa6 is ON HOLD until Paper Publication		The entry 5wa6 is ON HOLD until Paper Publication

-	Authors: Kumar, G., White, S.	+	Authors: Kumar, G., White, S.W.

	Description: Crystal structure of the influenza virus PA endonuclease in complex with an inhibitor -SRI-30007		Description: Crystal structure of the influenza virus PA endonuclease in complex with an inhibitor -SRI-30007
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: White, S]]	+	[[Category: White, S.W]]
	[[Category: Kumar, G]]		[[Category: Kumar, G]]

OCA: Protected "5wa6" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 14:36:58 GMT

Protected "5wa6" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:36, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wa6 is ON HOLD until Paper Publication Authors: Kumar, G., White, S. Description: Crystal structure of the influenza virus PA endonuclease in comp...

OCA — Wed, 27 Sep 2017 14:36:57 GMT

New page: '''Unreleased structure''' The entry 5wa6 is ON HOLD until Paper Publication Authors: Kumar, G., White, S. Description: Crystal structure of the influenza virus PA endonuclease in comp...

New page

'''Unreleased structure'''

The entry 5wa6 is ON HOLD until Paper Publication

Authors: Kumar, G., White, S.

Description: Crystal structure of the influenza virus PA endonuclease in complex with an inhibitor -SRI-30007
[[Category: Unreleased Structures]]
[[Category: White, S]]
[[Category: Kumar, G]]