View source for 6ft8


==Crystal structure of CLK1 in complex with inhibitor 8g==
<StructureSection load='6ft8' size='340' side='right' caption='[[6ft8]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ft8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FT8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FT8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E6T:3-(3-hydroxyphenyl)-1~{H}-pyrrolo[3,4-g]indol-8-one'>E6T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=6ft8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ft8 OCA], [http://pdbe.org/6ft8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ft8 RCSB], [http://www.ebi.ac.uk/pdbsum/6ft8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ft8 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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cdc2-like kinases (CLKs) represent a family of serine-threonine kinases involved in the regulation of splicing by phosphorylation of SR-proteins and other splicing factors. Although compounds acting against CLKs have been described, only a few show selectivity against dual-specificity tyrosine phosphorylation regulated-kinases (DYRKs). We here report a novel CLK inhibitor family based on a 6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one core scaffold. Within the series, 3-(3-chlorophenyl)-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (KuWal151) was identified as inhibitor of CLK1, CLK2 and CLK4 with a high selectivity margin towards DYRK kinases. The compound displayed a potent antiproliferative activity in an array of cultured cancer cell lines. The X-ray structure analyses of three members of the new compound class co-crystallized with CLK proteins corroborated a molecular binding mode predicted by docking studies.

Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype.,Walter A, Chaikuad A, Helmer R, Loaec N, Preu L, Ott I, Knapp S, Meijer L, Kunick C PLoS One. 2018 May 3;13(5):e0196761. doi: 10.1371/journal.pone.0196761., eCollection 2018. PMID:29723265<ref>PMID:29723265</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ft8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dual-specificity kinase]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Chaikuad, A]]
[[Category: Delft, F von]]
[[Category: Edwards, A M]]
[[Category: Knapp, S]]
[[Category: Kunick, C]]
[[Category: Structural genomic]]
[[Category: Walter, A]]
[[Category: Clk]]
[[Category: Inhibitor]]
[[Category: Kinase]]
[[Category: Sgc]]
[[Category: Splicing kinase]]
[[Category: Transferase]]