6i5l
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of CLK1 in complexed with furo[3,2-b]pyridine compound VN316 (derivative of compound 12h)== | |
| + | <StructureSection load='6i5l' size='340' side='right'caption='[[6i5l]], [[Resolution|resolution]] 2.55Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6i5l]] is a 3 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=6I5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I5L FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H3Q:3-(3-cyclobutylphenyl)-5-(1-methylpyrazol-4-yl)furo[3,2-b]pyridine'>H3Q</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6i5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i5l OCA], [https://pdbe.org/6i5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i5l RCSB], [https://www.ebi.ac.uk/pdbsum/6i5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i5l ProSAT]</span></td></tr> | ||
| + | </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 == | ||
| + | Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway. | ||
| - | + | Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway.,Nemec V, Hylsova M, Maier L, Flegel J, Sievers S, Ziegler S, Schroeder M, Berger BT, Chaikuad A, Valcikova B, Uldrijan S, Drapela S, Soucek K, Waldmann H, Knapp S, Paruch K Angew Chem Int Ed Engl. 2018 Dec 20. doi: 10.1002/anie.201810312. PMID:30569600<ref>PMID:30569600</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6i5l" style="background-color:#fffaf0;"></div> |
| - | [[Category: Arrowsmith | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Arrowsmith CH]] | ||
| + | [[Category: Bountra C]] | ||
| + | [[Category: Chaikuad A]] | ||
| + | [[Category: Edwards AM]] | ||
| + | [[Category: Knapp S]] | ||
| + | [[Category: Paruch K]] | ||
Current revision
Crystal structure of CLK1 in complexed with furo[3,2-b]pyridine compound VN316 (derivative of compound 12h)
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