6qty - Revision history

OCA at 12:08, 24 January 2024

OCA — Wed, 24 Jan 2024 12:08:39 GMT

←Older revision		Revision as of 12:08, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6qty' size='340' side='right'caption='[[6qty]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='6qty' size='340' side='right'caption='[[6qty]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qty]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QTY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qty]] 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=6QTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QTY FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=V25:ETHYL+3~~-~~[(E)-2-AMINO-1-CYANOETHENYL]-6~~,~~7-DICHLORO-1-METHYL-1H-INDOLE-2-CARBOXYLATE'>V25</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='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[2vag\|2vag]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V25:ETHYL+3-[(E)-2-AMINO-1-CYANOETHENYL]-6,7-DICHLORO-1-METHYL-1H-INDOLE-2-CARBOXYLATE'>V25</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CLK1, CLK ([https://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'>[https~~:~~//en.wikipedia.org/wiki/Dual~~-~~specificity_kinase Dual~~-~~specificity kinase~~], ~~with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qty OCA], [https://pdbe.org/6qty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qty RCSB], [https://www.ebi.ac.uk/pdbsum/6qty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qty 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=6qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qty OCA], [https://pdbe.org/6qty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qty RCSB], [https://www.ebi.ac.uk/pdbsum/6qty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qty ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dual-specificity kinase]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Domovich, Y]]	+	[[Category: Domovich Y]]
-	[[Category: Livnah, O]]	+	[[Category: Livnah O]]
-	~~[[Category: Clk1]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Splicing]]~~	+
-	~~[[Category: Viral infection~~]]	+

OCA at 10:41, 31 March 2021

OCA — Wed, 31 Mar 2021 10:41:44 GMT

←Older revision		Revision as of 10:41, 31 March 2021
Line 3:		Line 3:
	<StructureSection load='6qty' size='340' side='right'caption='[[6qty]], [[Resolution\|resolution]] 1.65Å' scene=''>		<StructureSection load='6qty' size='340' side='right'caption='[[6qty]], [[Resolution\|resolution]] 1.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qty]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QTY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QTY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qty]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QTY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=V25:ETHYL+3-[(E)-2-AMINO-1-CYANOETHENYL]-6,7-DICHLORO-1-METHYL-1H-INDOLE-2-CARBOXYLATE'>V25</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=V25:ETHYL+3-[(E)-2-AMINO-1-CYANOETHENYL]-6,7-DICHLORO-1-METHYL-1H-INDOLE-2-CARBOXYLATE'>V25</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2vag\|2vag]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2vag\|2vag]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CLK1, CLK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qty OCA], [~~http~~://pdbe.org/6qty PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qty RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qty PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qty ProSAT]</span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=6qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qty OCA], [https://pdbe.org/6qty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qty RCSB], [https://www.ebi.ac.uk/pdbsum/6qty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qty ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://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>	+	[[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 ==
		+	Cdc-like kinase 1 (CLK1) is a dual-specificity kinase capable of autophosphorylation on tyrosine residues and Ser/Thr phosphorylation of its substrates. CLK1 belongs to the CLK kinase family that regulates alternative splicing through phosphorylation of serine-arginine rich (SR) proteins. Recent studies have demonstrated that CLK1 has an important role in the replication of influenza A and chikungunya viruses. Furthermore, CLK1 was found to be relevant for the replication of HIV-1 and the West Nile virus, making CLK1 an interesting cellular candidate for the development of a host-directed antiviral therapy that might be efficient for treatment of newly emerging viruses. We describe here our attempts and detailed procedures to obtain the recombinant kinase domain of CLK1 in suitable amounts for crystallization in complex with specific inhibitors. The key solution for the reproducibility of crystals resides in devising and refining expression and purification protocols leading to homogeneous protein. Co-expression of CLK1 with lambda-phosphatase and careful purification has yielded crystals of CLK1 complexed with the KH-CB19 inhibitor that diffracted to 1.65 A. These results paved the path to the screening of more structures of CLK1 complexed compounds, leading to further optimization of their inhibitory activity. Moreover, since kinases are desired targets in numerous pathologies, the approach we report here, the co-expression of kinases with lambda-phosphatase, previously used in other kinases, can be adopted as a general protocol in numerous kinase targets for obtaining reproducible and homogenic non-phosphorylated (inactive) forms suitable for biochemical and structural studies thus facilitating the development of novel inhibitors.
		+
		+	Expression, purification and crystallization of CLK1 kinase - A potential target for antiviral therapy.,Dekel N, Eisenberg-Domovich Y, Karlas A, Meyer TF, Bracher F, Lebendiker M, Danieli T, Livnah O Protein Expr Purif. 2020 Dec;176:105742. doi: 10.1016/j.pep.2020.105742. Epub, 2020 Aug 29. PMID:32866611<ref>PMID:32866611</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qty" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dual specificity protein kinase 3D structures\|Dual specificity protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 16:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Dual-specificity kinase]]		[[Category: Dual-specificity kinase]]
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Domovich, Y]]		[[Category: Domovich, Y]]

OCA at 09:48, 18 March 2020

OCA — Wed, 18 Mar 2020 09:48:11 GMT

←Older revision		Revision as of 09:48, 18 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qty is ~~ON HOLD until Paper Publication~~	+	==Non-phosphorylated human CLK1 in complex with an indole inhibitor to 1.65 Ang==
-		+	<StructureSection load='6qty' size='340' side='right'caption='[[6qty]], [[Resolution\|resolution]] 1.65Å' scene=''>
-	~~Authors~~: ~~Livnah~~, O., ~~Domovich~~, Y.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qty]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QTY FirstGlance]. <br>
-	~~Description~~: ~~Non~~-~~phosphorylated human CLK1 in~~ complex ~~with an indole inhibitor~~ to 1.~~65 Ang~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=V25:ETHYL+3-[(E)-2-AMINO-1-CYANOETHENYL]-6,7-DICHLORO-1-METHYL-1H-INDOLE-2-CARBOXYLATE'>V25</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2vag\|2vag]]</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=6qty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qty OCA], [http://pdbe.org/6qty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qty RCSB], [http://www.ebi.ac.uk/pdbsum/6qty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qty ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dual-specificity kinase]]
		+	[[Category: Large Structures]]
	[[Category: Domovich, Y]]		[[Category: Domovich, Y]]
	[[Category: Livnah, O]]		[[Category: Livnah, O]]
		+	[[Category: Clk1]]
		+	[[Category: Kinase]]
		+	[[Category: Signaling protein]]
		+	[[Category: Splicing]]
		+	[[Category: Viral infection]]

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

OCA — Wed, 06 Mar 2019 05:54:25 GMT

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

←Older revision

Revision as of 05:54, 6 March 2019

OCA: New page: '''Unreleased structure''' The entry 6qty is ON HOLD until Paper Publication Authors: Livnah, O., Domovich, Y. Description: Non-phosphorylated human CLK1 in complex with an indole inhi...

OCA — Wed, 06 Mar 2019 05:54:23 GMT

New page: '''Unreleased structure''' The entry 6qty is ON HOLD until Paper Publication Authors: Livnah, O., Domovich, Y. Description: Non-phosphorylated human CLK1 in complex with an indole inhi...

New page

'''Unreleased structure'''

The entry 6qty is ON HOLD until Paper Publication

Authors: Livnah, O., Domovich, Y.

Description: Non-phosphorylated human CLK1 in complex with an indole inhibitor to 1.65 Ang
[[Category: Unreleased Structures]]
[[Category: Domovich, Y]]
[[Category: Livnah, O]]