5vpt - Revision history

OCA at 13:54, 4 October 2023

OCA — Wed, 04 Oct 2023 13:54:54 GMT

←Older revision		Revision as of 13:54, 4 October 2023
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	<StructureSection load='5vpt' size='340' side='right'caption='[[5vpt]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='5vpt' size='340' side='right'caption='[[5vpt]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vpt]] 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=5VPT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VPT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vpt]] 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=5VPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VPT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=R07:1-[(11S)-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-5-hydroxy-3-[(2R)-1,1,1-trifluoropropan-2-yl]-2,3-dihydro-1H-pyrido[2,1-f][1,2,4]triazine-4,6-dione'>R07</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]] 2.1Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vp8\|5vp8]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=R07:1-[(11S)-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-5-hydroxy-3-[(2R)-1,1,1-trifluoropropan-2-yl]-2,3-dihydro-1H-pyrido[2,1-f][1,2,4]triazine-4,6-dione'>R07</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5vpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vpt OCA], [https://pdbe.org/5vpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vpt RCSB], [https://www.ebi.ac.uk/pdbsum/5vpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vpt 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=5vpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vpt OCA], [~~http~~://pdbe.org/5vpt PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vpt RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vpt PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vpt ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/C3W5S0_I09A0 C3W5S0_I09A0]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[RNA polymerase\|RNA polymerase]]	+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<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: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Nuclease influenza inhibitor resistance~~]]	+

OCA at 09:37, 1 January 2020

OCA — Wed, 01 Jan 2020 09:37:49 GMT

←Older revision		Revision as of 09:37, 1 January 2020
Line 1:		Line 1:

	==2009 H1N1 PA Endonuclease in complex with RO-7==		==2009 H1N1 PA Endonuclease in complex with RO-7==
-	<StructureSection load='5vpt' size='340' side='right' caption='[[5vpt]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='5vpt' size='340' side='right'caption='[[5vpt]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vpt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VPT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VPT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vpt]] 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=5VPT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VPT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=R07:1-[(11S)-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-5-hydroxy-3-[(2R)-1,1,1-trifluoropropan-2-yl]-2,3-dihydro-1H-pyrido[2,1-f][1,2,4]triazine-4,6-dione'>R07</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=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=R07:1-[(11S)-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-5-hydroxy-3-[(2R)-1,1,1-trifluoropropan-2-yl]-2,3-dihydro-1H-pyrido[2,1-f][1,2,4]triazine-4,6-dione'>R07</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">[[5vp8\|5vp8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vp8\|5vp8]]</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=5vpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vpt OCA], [http://pdbe.org/5vpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vpt RCSB], [http://www.ebi.ac.uk/pdbsum/5vpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vpt 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=5vpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vpt OCA], [http://pdbe.org/5vpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vpt RCSB], [http://www.ebi.ac.uk/pdbsum/5vpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vpt ProSAT]</span></td></tr>
	</table>		</table>
Line 17:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5vpt" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vpt" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase\|RNA polymerase]]
	== References ==		== References ==
	<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]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Nuclease influenza inhibitor resistance]]		[[Category: Nuclease influenza inhibitor resistance]]

OCA at 06:28, 9 May 2018

OCA — Wed, 09 May 2018 06:28:18 GMT

←Older revision		Revision as of 06:28, 9 May 2018
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	<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=5vpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vpt OCA], [http://pdbe.org/5vpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vpt RCSB], [http://www.ebi.ac.uk/pdbsum/5vpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vpt 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=5vpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vpt OCA], [http://pdbe.org/5vpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vpt RCSB], [http://www.ebi.ac.uk/pdbsum/5vpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vpt ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The clinical severity and annual occurrence of influenza virus epidemics, combined with the availability of just a single class of antivirals to treat infections, underscores the urgent need to develop new anti-influenza drugs. The endonuclease activity within the viral acidic polymerase (PA) protein is an attractive target for drug discovery due to the critical role it plays in viral gene transcription. RO-7 is a next-generation PA endonuclease inhibitor of influenza A and B viruses, but its drug resistance potential is unknown. Through serial passage of influenza A(H1N1) viruses in MDCK cells under selective pressure of RO-7, we identified an I38T substitution within the PA endonuclease domain that conferred in vitro resistance to RO-7 (up to a 287-fold change in 50% effective concentration [EC50]). I38T emerged between 5 and 10 passages, and when introduced into recombinant influenza A(H1N1) viruses, alone conferred RO-7 resistance (up to an 81-fold change in EC50). Cocrystal structures of mutant and wild-type endonuclease domains with RO-7 provided the structural basis of resistance, where a key hydrophobic interaction between RO-7 and the Ile38 side chain is compromised when mutated to the polar threonine. While Ile38 does not have a crucial role in coordinating the endonuclease active site, the switch to threonine does affect the polymerase activity of some viruses and influences RO-7 affinity for the PAN target (i.e., the approximately 200-residue N-terminal domain of PA). However, the change does not lead to a complete loss of replication activity in vitro Our results predict that RO-7-resistant influenza viruses carrying the I38T substitution may emerge under treatment. This should be taken into consideration for clinical surveillance and in refinement of these drugs.IMPORTANCE The effectiveness of antiviral drugs can be severely compromised by the emergence of resistant viruses. Therefore, determination of the mechanisms by which viruses become resistant is critical for drug development and clinical use. RO-7 is a compound that potently inhibits influenza virus replication and belongs to a new class of drugs in late-stage clinical trials for treatment of influenza virus infection. Here we demonstrate that a single amino acid change acquired under prolonged virus exposure to RO-7 renders influenza viruses significantly less susceptible to its inhibitory effects. We have discovered how the mutation can simultaneously interfere with drug activity and still maintain efficient virus replication. These findings have important implications for the development of more effective derivatives of RO-7-like drugs and provide guidance for how to monitor the emergence of resistance.
		+
		+	Identification of the I38T PA Substitution as a Resistance Marker for Next-Generation Influenza Virus Endonuclease Inhibitors.,Jones JC, Kumar G, Barman S, Najera I, White SW, Webby RJ, Govorkova EA MBio. 2018 Apr 24;9(2). pii: mBio.00430-18. doi: 10.1128/mBio.00430-18. PMID:29691337<ref>PMID:29691337</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5vpt" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 13:46, 11 April 2018

OCA — Wed, 11 Apr 2018 13:46:05 GMT

←Older revision		Revision as of 13:46, 11 April 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5vpt is ~~ON HOLD until Paper Publication~~	+	==2009 H1N1 PA Endonuclease in complex with RO-7==
-		+	<StructureSection load='5vpt' size='340' side='right' caption='[[5vpt]], [[Resolution\|resolution]] 2.10Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5vpt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VPT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VPT FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=R07:1-[(11S)-6,11-dihydrodibenzo[b,e]thiepin-11-yl]-5-hydroxy-3-[(2R)-1,1,1-trifluoropropan-2-yl]-2,3-dihydro-1H-pyrido[2,1-f][1,2,4]triazine-4,6-dione'>R07</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vp8\|5vp8]]</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=5vpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vpt OCA], [http://pdbe.org/5vpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vpt RCSB], [http://www.ebi.ac.uk/pdbsum/5vpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vpt ProSAT]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Kumar, G]]
		+	[[Category: White, S W]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Nuclease influenza inhibitor resistance]]

OCA at 11:42, 24 May 2017

OCA — Wed, 24 May 2017 11:42:50 GMT

←Older revision		Revision as of 11:42, 24 May 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5vpt is ON HOLD	+	The entry 5vpt is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 17 May 2017 14:05:48 GMT

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

←Older revision

Revision as of 14:05, 17 May 2017

OCA: New page: '''Unreleased structure''' The entry 5vpt is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 May 2017 14:05:47 GMT

New page: '''Unreleased structure''' The entry 5vpt is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5vpt is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]