6fyr - Revision history

OCA at 07:54, 12 September 2018

OCA — Wed, 12 Sep 2018 07:54:46 GMT

←Older revision		Revision as of 07:54, 12 September 2018
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	<StructureSection load='6fyr' size='340' side='right' caption='[[6fyr]], [[Resolution\|resolution]] 1.42Å' scene=''>		<StructureSection load='6fyr' size='340' side='right' caption='[[6fyr]], [[Resolution\|resolution]] 1.42Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6fyr]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FYR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FYR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6fyr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FYR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FYR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EAQ:6-~{tert}-butyl-~{N}-[6-(1~{H}-pyrazol-4-yl)-1~{H}-imidazo[1,2-a]pyridin-2-yl]pyridine-3-carboxamide'>EAQ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EAQ:6-~{tert}-butyl-~{N}-[6-(1~{H}-pyrazol-4-yl)-1~{H}-imidazo[1,2-a]pyridin-2-yl]pyridine-3-carboxamide'>EAQ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6fyi\|6fyi]], [[6fyk\|6fyk]], [[6fyl\|6fyl]], [[6fyo\|6fyo]], [[6fyp\|6fyp]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6fyi\|6fyi]], [[6fyk\|6fyk]], [[6fyl\|6fyl]], [[6fyo\|6fyo]], [[6fyp\|6fyp]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CLK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </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=6fyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fyr OCA], [http://pdbe.org/6fyr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fyr RCSB], [http://www.ebi.ac.uk/pdbsum/6fyr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fyr 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=6fyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fyr OCA], [http://pdbe.org/6fyr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fyr RCSB], [http://www.ebi.ac.uk/pdbsum/6fyr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fyr ProSAT]</span></td></tr>
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	</StructureSection>		</StructureSection>
	[[Category: Dual-specificity kinase]]		[[Category: Dual-specificity kinase]]
		+	[[Category: Human]]
	[[Category: Kallen, J]]		[[Category: Kallen, J]]
	[[Category: Kinase]]		[[Category: Kinase]]

OCA at 07:42, 18 July 2018

OCA — Wed, 18 Jul 2018 07:42:29 GMT

←Older revision		Revision as of 07:42, 18 July 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6fyr is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==X-RAY STRUCTURE OF CLK3-KD(GP-[275-632], NON-PHOS.)/Cpd-2 AT 1.42A==
		+	<StructureSection load='6fyr' size='340' side='right' caption='[[6fyr]], [[Resolution\|resolution]] 1.42Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6fyr]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FYR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FYR FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EAQ:6-~{tert}-butyl-~{N}-[6-(1~{H}-pyrazol-4-yl)-1~{H}-imidazo[1,2-a]pyridin-2-yl]pyridine-3-carboxamide'>EAQ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6fyi\|6fyi]], [[6fyk\|6fyk]], [[6fyl\|6fyl]], [[6fyo\|6fyo]], [[6fyp\|6fyp]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </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=6fyr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fyr OCA], [http://pdbe.org/6fyr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fyr RCSB], [http://www.ebi.ac.uk/pdbsum/6fyr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fyr ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CLK3_HUMAN CLK3_HUMAN]] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:9637771</ref> <ref>PMID:19168442</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	CLK2 inhibition has been proposed as a potential mechanism to improve autism and neuronal functions in Phelan-McDermid syndrome (PMDS). Herein, we report the discovery of a very potent indazole CLK inhibitor series, and the CLK2 X-ray structure of its most potent analog. This new indazole series was identified via a biochemical CLK2 Caliper assay screen with 30k compounds that were selected by an in silico approach. Novel high resolution X-ray structures of all CLKs, including the first CLK4 X-ray structure, bound to known CLK2 inhibitor tool compounds (e.g. TG003, CX-4945), are also shown and yield insights into inhibitor selectivity in the CLK family. Efficacy of our new CLK2 inhibitors from the indazole series was demonstrated in the mouse brain slice assay, and potential safety concerns were investigated. We show genotoxicity findings in the human lymphocyte MNT assay using two structurally different CLK inhibitors, which reveals a major concern for pan-CLK inhibition in PMDS.

-	~~Authors:~~ Kallen, J.	+	X-ray structures and feasibility assessment of CLK2 inhibitors for Phelan McDermid syndrome.,Lerchner AM, Kallen J, Bergsdorf C, Arnaud B, Bernhard M, Brichet M, Cobos-Correa A, Elhajouji A, Freuler F, Galimberti I, Guibourdenche C, Haenni S, Holzinger S, Hunziker J, Izaac A, Kaufmann M, Leder L, Martus HJ, von Matt P, Polyakov V, Roethlisberger P, Roma G, Stiefl N, Uteng M ChemMedChem. 2018 Jul 9. doi: 10.1002/cmdc.201800344. PMID:29985556<ref>PMID:29985556</ref>

-	~~Description: X-RAY STRUCTURE OF CLK3-KD(GP-[275-632]~~, ~~NON-PHOS~~.)/~~Cpd~~-~~2 AT 1.42A~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6fyr" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dual-specificity kinase]]
	[[Category: Kallen, J]]		[[Category: Kallen, J]]
		+	[[Category: Kinase]]
		+	[[Category: Nucleotide-binding]]
		+	[[Category: Serine/ threonine- protein kinase]]
		+	[[Category: Splicing]]
		+	[[Category: Transferase]]
		+	[[Category: Tyrosine-protein kinase]]

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

OCA — Wed, 21 Mar 2018 06:21:34 GMT

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

←Older revision

Revision as of 06:21, 21 March 2018

OCA: New page: '''Unreleased structure''' The entry 6fyr is ON HOLD until Paper Publication Authors: Kallen, J. Description: X-RAY STRUCTURE OF CLK3-KD(GP-[275-632], NON-PHOS.)/Cpd-2 AT 1.42A [[Categ...

OCA — Wed, 21 Mar 2018 06:21:33 GMT

New page: '''Unreleased structure''' The entry 6fyr is ON HOLD until Paper Publication Authors: Kallen, J. Description: X-RAY STRUCTURE OF CLK3-KD(GP-[275-632], NON-PHOS.)/Cpd-2 AT 1.42A [[Categ...

New page

'''Unreleased structure'''

The entry 6fyr is ON HOLD until Paper Publication

Authors: Kallen, J.

Description: X-RAY STRUCTURE OF CLK3-KD(GP-[275-632], NON-PHOS.)/Cpd-2 AT 1.42A
[[Category: Unreleased Structures]]
[[Category: Kallen, J]]