7nuh - Revision history

OCA at 12:40, 1 February 2024

OCA — Thu, 01 Feb 2024 12:40:05 GMT

←Older revision		Revision as of 12:40, 1 February 2024
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	<StructureSection load='7nuh' size='340' side='right'caption='[[7nuh]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='7nuh' size='340' side='right'caption='[[7nuh]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7nuh]] 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=7NUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NUH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7nuh]] 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=7NUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NUH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=USE:Orientin'>USE</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]] 2.2Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=USE:Orientin'>USE</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=7nuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nuh OCA], [https://pdbe.org/7nuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nuh RCSB], [https://www.ebi.ac.uk/pdbsum/7nuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nuh 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=7nuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nuh OCA], [https://pdbe.org/7nuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nuh RCSB], [https://www.ebi.ac.uk/pdbsum/7nuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nuh ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/C3W5X6_9INFA C3W5X6_9INFA]] Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.[HAMAP-Rule:MF_04063]	+	[https://www.uniprot.org/uniprot/C3W5X6_9INFA C3W5X6_9INFA] Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.[HAMAP-Rule:MF_04063]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brynda, J]]	+	[[Category: Brynda J]]
-	[[Category: Radilova, K]]	+	[[Category: Radilova K]]
-	~~[[Category: Endonuclease]]~~	+
-	~~[[Category: Flavonoid]]~~	+
-	~~[[Category: Protein-ligand complex]]~~	+
-	~~[[Category: Rna polymerase]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 10:36, 4 August 2021

OCA — Wed, 04 Aug 2021 10:36:38 GMT

←Older revision		Revision as of 10:36, 4 August 2021
Line 1:		Line 1:

	==Influenza A/California/07/2009(H1N1) endonuclease with I38T mutation in complex with orientin==		==Influenza A/California/07/2009(H1N1) endonuclease with I38T mutation in complex with orientin==
-	<StructureSection load='7nuh' size='340' side='right'caption='[[7nuh]]' scene=''>	+	<StructureSection load='7nuh' size='340' side='right'caption='[[7nuh]], [[Resolution\|resolution]] 2.20Å' 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=7NUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NUH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7nuh]] 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=7NUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NUH 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=7nuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nuh OCA], [https://pdbe.org/7nuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nuh RCSB], [https://www.ebi.ac.uk/pdbsum/7nuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nuh 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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=USE:Orientin'>USE</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([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=7nuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nuh OCA], [https://pdbe.org/7nuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nuh RCSB], [https://www.ebi.ac.uk/pdbsum/7nuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nuh ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/C3W5X6_9INFA C3W5X6_9INFA]] Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.[HAMAP-Rule:MF_04063]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including the FDA-approved drug Xofluza. A general feature of endonuclease inhibitors is their ability to chelate Mg(2+) or Mn(2+) ions located in the enzyme's catalytic site. Previously, we screened a panel of flavonoids for PA inhibition and found luteolin and its C-glucoside orientin to be potent inhibitors. Through structural analysis, we identified the presence of a 3',4'-dihydroxyphenyl moiety as a crucial feature for sub-micromolar inhibitory activity. Here, we report results from a subsequent investigation exploring structural changes at the C-7 and C-8 positions of luteolin. Experimental IC50 values were determined by AlphaScreen technology. The most potent inhibitors were C-8 derivatives with inhibitory potencies comparable to that of luteolin. Bio-isosteric replacement of the C-7 hydroxyl moiety of luteolin led to a series of compounds with one-order-of-magnitude-lower inhibitory potencies. Using X-ray crystallography, we solved structures of the wild-type PA-N-terminal domain and its I38T mutant in complex with orientin at 1.9 A and 2.2 A resolution, respectively.
		+
		+	Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors.,Reiberger R, Radilova K, Kral M, Zima V, Majer P, Brynda J, Dracinsky M, Konvalinka J, Kozisek M, Machara A Int J Mol Sci. 2021 Jul 20;22(14). pii: ijms22147735. doi: 10.3390/ijms22147735. PMID:34299354<ref>PMID:34299354</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7nuh" 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: Endonuclease]]
		+	[[Category: Flavonoid]]
		+	[[Category: Protein-ligand complex]]
		+	[[Category: Rna polymerase]]
		+	[[Category: Viral protein]]

OCA at 10:35, 28 July 2021

OCA — Wed, 28 Jul 2021 10:35:38 GMT

←Older revision		Revision as of 10:35, 28 July 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7nuh is ON HOLD until Paper Publication~~	+	==Influenza A/California/07/2009(H1N1) endonuclease with I38T mutation in complex with orientin==
-		+	<StructureSection load='7nuh' size='340' side='right'caption='[[7nuh]]' 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=7NUH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NUH FirstGlance]. <br>
-	~~Description:~~ Influenza A/California/07/2009(H1N1) endonuclease with I38T mutation in complex with orientin	+	</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=7nuh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nuh OCA], [https://pdbe.org/7nuh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nuh RCSB], [https://www.ebi.ac.uk/pdbsum/7nuh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nuh 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 13:35, 2 June 2021

OCA — Wed, 02 Jun 2021 13:35:29 GMT

←Older revision		Revision as of 13:35, 2 June 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

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

OCA at 08:04, 26 May 2021

OCA — Wed, 26 May 2021 08:04:14 GMT

←Older revision		Revision as of 08:04, 26 May 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7nuh is ON HOLD ~~until Paper Publication~~	+	The entry 7nuh is ON HOLD

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

OCA at 04:22, 28 April 2021

OCA — Wed, 28 Apr 2021 04:22:36 GMT

←Older revision		Revision as of 04:22, 28 April 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

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

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

OCA — Wed, 17 Mar 2021 05:38:03 GMT

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

←Older revision

Revision as of 05:38, 17 March 2021

OCA: New page: '''Unreleased structure''' The entry 7nuh is ON HOLD Authors: Radilova, K., Brynda, J. Description: Influenza A/California/07/2009(H1N1) endonuclease with I38T mutation in complex with...

OCA — Wed, 17 Mar 2021 05:38:02 GMT

New page: '''Unreleased structure''' The entry 7nuh is ON HOLD Authors: Radilova, K., Brynda, J. Description: Influenza A/California/07/2009(H1N1) endonuclease with I38T mutation in complex with...

New page

'''Unreleased structure'''

The entry 7nuh is ON HOLD

Authors: Radilova, K., Brynda, J.

Description: Influenza A/California/07/2009(H1N1) endonuclease with I38T mutation in complex with orientin
[[Category: Unreleased Structures]]
[[Category: Radilova, K]]
[[Category: Brynda, J]]