7as3 - Revision history

OCA at 12:15, 1 February 2024

2024-02-01T12:15:17Z

←Older revision		Revision as of 12:15, 1 February 2024
Line 3:		Line 3:
	<StructureSection load='7as3' size='340' side='right'caption='[[7as3]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='7as3' size='340' side='right'caption='[[7as3]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7as3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Influenza_a_virus_~~(a/~~california~~/07/2009(~~h1n1~~)) Influenza a virus (a/~~california~~/07/2009(~~h1n1~~))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AS3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7as3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/California/07/2009(H1N1)) Influenza A virus (A/California/07/2009(H1N1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AS3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21G:(2S,3S)-3-[[5-FLUORANYL-2-(5-FLUORANYL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PYRIMIDIN-4-YL]AMINO]BICYCLO[2.2.2]OCTANE-2-CARBOXYLIC+ACID'>21G</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]] 1.65Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PB2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=641809 Influenza A virus (A/California/07/2009(H1N1))])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21G:(2S,3S)-3-[[5-FLUORANYL-2-(5-FLUORANYL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PYRIMIDIN-4-YL]AMINO]BICYCLO[2.2.2]OCTANE-2-CARBOXYLIC+ACID'>21G</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=7as3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7as3 OCA], [https://pdbe.org/7as3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7as3 RCSB], [https://www.ebi.ac.uk/pdbsum/7as3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7as3 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=7as3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7as3 OCA], [https://pdbe.org/7as3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7as3 RCSB], [https://www.ebi.ac.uk/pdbsum/7as3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7as3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/C3W5X5_9INFA C3W5X5_9INFA]] Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex.[HAMAP-Rule:MF_04062]	+	[https://www.uniprot.org/uniprot/C3W5X5_9INFA C3W5X5_9INFA] Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex.[HAMAP-Rule:MF_04062]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 7as3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7as3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brynda, J]]	+	[[Category: Brynda J]]
-	[[Category: Radilova, K]]	+	[[Category: Radilova K]]
-	~~[[Category: Influenza some]]~~	+
-	~~[[Category: Polymerase]]~~	+
-	~~[[Category: Polymerase basic protein 2]]~~	+
-	~~[[Category: Viral protein]]~~	+
-	~~[[Category: Vx787~~]]	+

OCA at 06:57, 17 March 2021

2021-03-17T06:57:10Z

←Older revision		Revision as of 06:57, 17 March 2021
Line 1:		Line 1:

	==Influenza A PB2 (H357N mutation) in complex with VX-787==		==Influenza A PB2 (H357N mutation) in complex with VX-787==
-	<StructureSection load='7as3' size='340' side='right'caption='[[7as3]]' scene=''>	+	<StructureSection load='7as3' size='340' side='right'caption='[[7as3]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AS3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7as3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_a_virus_(a/california/07/2009(h1n1)) Influenza a virus (a/california/07/2009(h1n1))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AS3 FirstGlance]. <br>
-	</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=7as3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7as3 OCA], [https://pdbe.org/7as3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7as3 RCSB], [https://www.ebi.ac.uk/pdbsum/7as3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7as3 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21G:(2S,3S)-3-[[5-FLUORANYL-2-(5-FLUORANYL-1H-PYRROLO[2,3-B]PYRIDIN-3-YL)PYRIMIDIN-4-YL]AMINO]BICYCLO[2.2.2]OCTANE-2-CARBOXYLIC+ACID'>21G</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PB2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=641809 Influenza A virus (A/California/07/2009(H1N1))])</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=7as3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7as3 OCA], [https://pdbe.org/7as3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7as3 RCSB], [https://www.ebi.ac.uk/pdbsum/7as3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7as3 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/C3W5X5_9INFA C3W5X5_9INFA]] Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex.[HAMAP-Rule:MF_04062]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Influenza A virus (IAV) encodes a polymerase composed of three subunits: PA, with endonuclease activity, PB1 with polymerase activity and PB2 with host RNA five-prime cap binding site. Their cooperation and stepwise activation include a process called cap-snatching, which is a crucial step in the IAV life cycle. Reproduction of IAV can be blocked by disrupting the interaction between the PB2 domain and the five-prime cap. An inhibitor of this interaction called pimodivir (VX-787) recently entered the third phase of clinical trial; however, several mutations in PB2 that cause resistance to pimodivir were observed. First major mutation, F404Y, causing resistance was identified during preclinical testing, next the mutation M431I was identified in patients during the second phase of clinical trials. The mutation H357N was identified during testing of IAV strains at Centers for Disease Control and Prevention. We set out to provide a structural and thermodynamic analysis of the interactions between cap-binding domain of PB2 wild-type and PB2 variants bearing these mutations and pimodivir. Here we present four crystal structures of PB2-WT, PB2-F404Y, PB2-M431I and PB2-H357N in complex with pimodivir. We have thermodynamically analysed all PB2 variants and proposed the effect of these mutations on thermodynamic parameters of these interactions and pimodivir resistance development. These data will contribute to understanding the effect of these missense mutations to the resistance development and help to design next generation inhibitors.
		+
		+	Structural and Thermodynamic Analysis of the Resistance Development to Pimodivir (VX-787), the Clinical Inhibitor of Cap Binding to PB2 Subunit of Influenza A Polymerase.,Gregor J, Radilova K, Brynda J, Fanfrlik J, Konvalinka J, Kozisek M Molecules. 2021 Feb 14;26(4). pii: molecules26041007. doi:, 10.3390/molecules26041007. PMID:33673017<ref>PMID:33673017</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7as3" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brynda J]]	+	[[Category: Brynda, J]]
-	[[Category: Radilova K]]	+	[[Category: Radilova, K]]
		+	[[Category: Influenza some]]
		+	[[Category: Polymerase]]
		+	[[Category: Polymerase basic protein 2]]
		+	[[Category: Viral protein]]
		+	[[Category: Vx787]]

OCA at 06:39, 24 February 2021

2021-02-24T06:39:48Z

←Older revision		Revision as of 06:39, 24 February 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7as3 is ON HOLD until Paper Publication~~	+	==Influenza A PB2 (H357N mutation) in complex with VX-787==
-		+	<StructureSection load='7as3' size='340' side='right'caption='[[7as3]]' scene=''>
-	~~Authors: Radilova, K., Brynda, J.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AS3 FirstGlance]. <br>
-	~~Description:~~ Influenza A PB2 (H357N mutation) in complex with VX-787	+	</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=7as3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7as3 OCA], [https://pdbe.org/7as3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7as3 RCSB], [https://www.ebi.ac.uk/pdbsum/7as3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7as3 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Radilova~~, K]]	+	__TOC__
-	[[Category: Brynda, J]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Brynda J]]
		+	[[Category: Radilova K]]

OCA at 05:28, 2 December 2020

2020-12-02T05:28:27Z

←Older revision		Revision as of 05:28, 2 December 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7as3 is ON HOLD	+	The entry 7as3 is ON HOLD until Paper Publication

	Authors: Radilova, K., Brynda, J.		Authors: Radilova, K., Brynda, J.

OCA at 07:51, 18 November 2020

2020-11-18T07:51:09Z

←Older revision		Revision as of 07:51, 18 November 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7as3 is ON HOLD ~~until sometime in the future~~	+	The entry 7as3 is ON HOLD

	Authors: Radilova, K., Brynda, J.		Authors: Radilova, K., Brynda, J.

OCA: Protected "7as3" [edit=sysop:move=sysop]

2020-11-04T05:22:53Z

Protected "7as3" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:22, 4 November 2020

OCA: New page: '''Unreleased structure''' The entry 7as3 is ON HOLD until sometime in the future Authors: Radilova, K., Brynda, J. Description: Influenza A PB2 (H357N mutation) in complex with VX-787...

2020-11-04T05:22:52Z

New page: '''Unreleased structure''' The entry 7as3 is ON HOLD until sometime in the future Authors: Radilova, K., Brynda, J. Description: Influenza A PB2 (H357N mutation) in complex with VX-787...

New page

'''Unreleased structure'''

The entry 7as3 is ON HOLD until sometime in the future

Authors: Radilova, K., Brynda, J.

Description: Influenza A PB2 (H357N mutation) in complex with VX-787
[[Category: Unreleased Structures]]
[[Category: Radilova, K]]
[[Category: Brynda, J]]