6va3 - Revision history

OCA at 07:11, 16 March 2022

OCA — Wed, 16 Mar 2022 07:11:22 GMT

←Older revision		Revision as of 07:11, 16 March 2022
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	<StructureSection load='6va3' size='340' side='right'caption='[[6va3]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='6va3' size='340' side='right'caption='[[6va3]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6va3]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VA3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6VA3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6va3]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VA3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VA3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MQC:4-[(3-methoxyphenyl)amino]-2-methylquinoline-6-carboximidamide'>MQC</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MQC:4-[(3-methoxyphenyl)amino]-2-methylquinoline-6-carboximidamide'>MQC</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6va3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6va3 OCA], [~~http~~://pdbe.org/6va3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6va3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6va3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6va3 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=6va3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6va3 OCA], [https://pdbe.org/6va3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6va3 RCSB], [https://www.ebi.ac.uk/pdbsum/6va3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6va3 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:37, 27 May 2020

OCA — Wed, 27 May 2020 07:37:23 GMT

←Older revision		Revision as of 07:37, 27 May 2020
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	==Solution Structure of the Tau pre-mRNA Exon 10 Splicing Regulatory Element Bound to MQC==		==Solution Structure of the Tau pre-mRNA Exon 10 Splicing Regulatory Element Bound to MQC==
-	<StructureSection load='6va3' size='340' side='right'caption='[[6va3]]' scene=''>	+	<StructureSection load='6va3' size='340' side='right'caption='[[6va3]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' 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=6VA3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VA3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6va3]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VA3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VA3 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6va3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6va3 OCA], [http://pdbe.org/6va3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6va3 RCSB], [http://www.ebi.ac.uk/pdbsum/6va3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6va3 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=MQC:4-[(3-methoxyphenyl)amino]-2-methylquinoline-6-carboximidamide'>MQC</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6va3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6va3 OCA], [http://pdbe.org/6va3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6va3 RCSB], [http://www.ebi.ac.uk/pdbsum/6va3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6va3 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Approximately 95% of human genes are alternatively spliced, and aberrant splicing events can cause disease. One pre-mRNA that is alternatively spliced and linked to neurodegenerative diseases is tau (microtubule-associated protein tau), which can cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and can contribute to Alzheimer's disease. Here, we describe the design of structure-specific lead small molecules that directly target tau pre-mRNA from sequence. This was followed by hit expansion and analogue synthesis to further improve upon these initial lead molecules. The emergent compounds were assessed for functional activity in a battery of assays, including binding assays and an assay that mimics molecular recognition of tau pre-mRNA by a U1 small nuclear ribonucleoprotein (snRNP) splicing factor. Compounds that emerged from these studies had enhanced potency and selectivity for the target RNA relative to the initial hits, while also having significantly improved drug-like properties. The compounds are shown to directly target tau pre-mRNA in cells, via chemical cross-linking and isolation by pull-down target profiling, and to rescue disease-relevant splicing of tau pre-mRNA in a variety of cellular systems, including primary neurons. More broadly, this study shows that lead, structure-specific compounds can be designed from sequence and then further optimized for their physicochemical properties while at the same time enhancing their activity.
		+
		+	Design, Optimization, and Study of Small Molecules That Target Tau Pre-mRNA and Affect Splicing.,Chen JL, Zhang P, Abe M, Aikawa H, Zhang L, Frank AJ, Zembryski T, Hubbs C, Park H, Withka J, Steppan C, Rogers L, Cabral S, Pettersson M, Wager TT, Fountain MA, Rumbaugh G, Childs-Disney JL, Disney MD J Am Chem Soc. 2020 May 13;142(19):8706-8727. doi: 10.1021/jacs.0c00768. Epub, 2020 May 4. PMID:32364710<ref>PMID:32364710</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6va3" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen JL]]	+	[[Category: Chen, J L]]
-	[[Category: Disney MD]]	+	[[Category: Disney, M D]]
-	[[Category: Fountain MA]]	+	[[Category: Fountain, M A]]
		+	[[Category: A-form tau rna hairpin]]
		+	[[Category: Adenine bulge]]
		+	[[Category: Rna]]
		+	[[Category: Rna complex]]

OCA at 05:49, 20 May 2020

OCA — Wed, 20 May 2020 05:49:45 GMT

←Older revision		Revision as of 05:49, 20 May 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6va3 ~~is ON HOLD until Paper Publication~~	+	==Solution Structure of the Tau pre-mRNA Exon 10 Splicing Regulatory Element Bound to MQC==
-		+	<StructureSection load='6va3' size='340' side='right'caption='[[6va3]]' scene=''>
-	~~Authors~~: ~~Chen~~, J.L., ~~Fountain~~, M.A., ~~Disney~~, M.D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VA3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VA3 FirstGlance]. <br>
-	~~Description: Solution Structure of the Tau pre-mRNA Exon 10 Splicing Regulatory Element Bound to MQC~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6va3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6va3 OCA], [http://pdbe.org/6va3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6va3 RCSB], [http://www.ebi.ac.uk/pdbsum/6va3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6va3 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Disney, M.D~~]]	+	__TOC__
-	[[Category: ~~Chen, J.L~~]]	+	</StructureSection>
-	[[Category: Fountain~~, M.A~~]]	+	[[Category: Large Structures]]
		+	[[Category: Chen JL]]
		+	[[Category: Disney MD]]
		+	[[Category: Fountain MA]]

OCA at 14:15, 22 January 2020

OCA — Wed, 22 Jan 2020 14:15:35 GMT

←Older revision		Revision as of 14:15, 22 January 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6va3 is ON HOLD	+	The entry 6va3 is ON HOLD until Paper Publication

	Authors: Chen, J.L., Fountain, M.A., Disney, M.D.		Authors: Chen, J.L., Fountain, M.A., Disney, M.D.

OCA: Protected "6va3" [edit=sysop:move=sysop]

OCA — Wed, 25 Dec 2019 07:34:12 GMT

Protected "6va3" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:34, 25 December 2019

OCA: New page: '''Unreleased structure''' The entry 6va3 is ON HOLD Authors: Chen, J.L., Fountain, M.A., Disney, M.D. Description: Solution Structure of the Tau pre-mRNA Exon 10 Splicing Regulatory E...

OCA — Wed, 25 Dec 2019 07:34:10 GMT

New page: '''Unreleased structure''' The entry 6va3 is ON HOLD Authors: Chen, J.L., Fountain, M.A., Disney, M.D. Description: Solution Structure of the Tau pre-mRNA Exon 10 Splicing Regulatory E...

New page

'''Unreleased structure'''

The entry 6va3 is ON HOLD

Authors: Chen, J.L., Fountain, M.A., Disney, M.D.

Description: Solution Structure of the Tau pre-mRNA Exon 10 Splicing Regulatory Element Bound to MQC
[[Category: Unreleased Structures]]
[[Category: Disney, M.D]]
[[Category: Chen, J.L]]
[[Category: Fountain, M.A]]