6yta - Revision history

OCA at 13:35, 24 January 2024

OCA — Wed, 24 Jan 2024 13:35:04 GMT

←Older revision		Revision as of 13:35, 24 January 2024
Line 1:		Line 1:

	==CLK1 bound with imidazopyridazine (Cpd 1)==		==CLK1 bound with imidazopyridazine (Cpd 1)==
-	<StructureSection load='6yta' size='340' side='right'caption='[[6yta]]' scene=''>	+	<StructureSection load='6yta' size='340' side='right'caption='[[6yta]], [[Resolution\|resolution]] 2.30Å' 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=6YTA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6YTA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6yta]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YTA 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=6yta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yta OCA], [~~http~~://pdbe.org/6yta PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6yta RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6yta PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6yta ProSAT]</span></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]] 2.3Å</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=IYZ:1-(3-{6-[(CYCLOPROPYLMETHYL)AMINO]IMIDAZO[1,2-B]PYRIDAZIN-3-YL}PHENYL)ETHANONE'>IYZ</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=6yta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yta OCA], [https://pdbe.org/6yta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yta RCSB], [https://www.ebi.ac.uk/pdbsum/6yta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yta ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/CLK1_HUMAN CLK1_HUMAN] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Selectivity remains a challenge for ATP-mimetic kinase inhibitors, an issue that may be overcome by targeting unique residues or binding pockets. However, to date only few strategies have been developed. Here we identify that bulky residues located N-terminal to the DFG motif (DFG-1) represent an opportunity for designing highly selective inhibitors with unexpected binding modes. We demonstrate that several diverse inhibitors exerted selective, noncanonical binding modes that exclusively target large hydrophobic DFG-1 residues present in many kinases including PIM, CK1, DAPK, and CLK. By use of the CLK family as a model, structural and biochemical data revealed that the DFG-1 valine controlled a noncanonical binding mode in CLK1, providing a rationale for selectivity over the closely related CLK3 which harbors a smaller DFG-1 alanine. Our data suggest that targeting the restricted back pocket in the small fraction of kinases that harbor bulky DFG-1 residues offers a versatile selectivity filter for inhibitor design.
		+
		+	DFG-1 Residue Controls Inhibitor Binding Mode and Affinity, Providing a Basis for Rational Design of Kinase Inhibitor Selectivity.,Schroder M, Bullock AN, Fedorov O, Bracher F, Chaikuad A, Knapp S J Med Chem. 2020 Sep 24;63(18):10224-10234. doi: 10.1021/acs.jmedchem.0c00898., Epub 2020 Aug 27. PMID:32787076<ref>PMID:32787076</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6yta" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dual specificity protein kinase 3D structures\|Dual specificity protein kinase 3D structures]]		*[[Dual specificity protein kinase 3D structures\|Dual specificity protein kinase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chaikuad A]]		[[Category: Chaikuad A]]
	[[Category: Knapp S]]		[[Category: Knapp S]]
	[[Category: Schroeder M]]		[[Category: Schroeder M]]

OCA at 06:17, 14 October 2020

OCA — Wed, 14 Oct 2020 06:17:54 GMT

←Older revision		Revision as of 06:17, 14 October 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6yta is ~~ON HOLD~~	+	==CLK1 bound with imidazopyridazine (Cpd 1)==
		+	<StructureSection load='6yta' size='340' side='right'caption='[[6yta]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YTA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YTA 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=6yta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yta OCA], [http://pdbe.org/6yta PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yta RCSB], [http://www.ebi.ac.uk/pdbsum/6yta PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yta ProSAT]</span></td></tr>
		+	</table>

-	~~Authors: Schroeder, M., Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC)~~	+	==See Also==
-		+	*[[Dual specificity protein kinase 3D structures\|Dual specificity protein kinase 3D structures]]
-	~~Description: CLK1 bound with imidazopyridazine (Cpd 1)~~	+	__TOC__
-	[[Category: ~~Unreleased~~ Structures]]	+	</StructureSection>
-	[[Category: Chaikuad, A]]	+	[[Category: Large Structures]]
-	[[Category: Knapp, S]]	+	[[Category: Chaikuad A]]
-	~~[[Category: Structural Genomics Consortium (Sgc)~~]]	+	[[Category: Knapp S]]
-	[[Category: Schroeder, M]]	+	[[Category: Schroeder M]]

OCA at 04:38, 6 May 2020

OCA — Wed, 06 May 2020 04:38:43 GMT

←Older revision		Revision as of 04:38, 6 May 2020
Line 3:		Line 3:
	The entry 6yta is ON HOLD		The entry 6yta is ON HOLD

-	Authors: Schroeder, M., Chaikuad, A., Knapp, S.	+	Authors: Schroeder, M., Chaikuad, A., Knapp, S., Structural Genomics Consortium (SGC)

	Description: CLK1 bound with imidazopyridazine (Cpd 1)		Description: CLK1 bound with imidazopyridazine (Cpd 1)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Chaikuad, A]]		[[Category: Chaikuad, A]]
-	[[Category: Schroeder, M]]
	[[Category: Knapp, S]]		[[Category: Knapp, S]]
		+	[[Category: Structural Genomics Consortium (Sgc)]]
		+	[[Category: Schroeder, M]]

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

OCA — Wed, 29 Apr 2020 05:32:41 GMT

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

←Older revision

Revision as of 05:32, 29 April 2020

OCA: New page: '''Unreleased structure''' The entry 6yta is ON HOLD Authors: Schroeder, M., Chaikuad, A., Knapp, S. Description: CLK1 bound with imidazopyridazine (Cpd 1) [[Category: Unreleased Struc...

OCA — Wed, 29 Apr 2020 05:32:39 GMT

New page: '''Unreleased structure''' The entry 6yta is ON HOLD Authors: Schroeder, M., Chaikuad, A., Knapp, S. Description: CLK1 bound with imidazopyridazine (Cpd 1) [[Category: Unreleased Struc...

New page

'''Unreleased structure'''

The entry 6yta is ON HOLD

Authors: Schroeder, M., Chaikuad, A., Knapp, S.

Description: CLK1 bound with imidazopyridazine (Cpd 1)
[[Category: Unreleased Structures]]
[[Category: Chaikuad, A]]
[[Category: Schroeder, M]]
[[Category: Knapp, S]]