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6i5h

From Proteopedia

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Crystal structure of CLK1 in complex with furanopyrimidin VN412

Structural highlights

6i5h is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.49Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Moeslein FM, Myers MP, Landreth GE. The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. J Biol Chem. 1999 Sep 17;274(38):26697-704. PMID:10480872
↑ Eisenreich A, Bogdanov VY, Zakrzewicz A, Pries A, Antoniak S, Poller W, Schultheiss HP, Rauch U. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. Circ Res. 2009 Mar 13;104(5):589-99. doi: 10.1161/CIRCRESAHA.108.183905. Epub, 2009 Jan 22. PMID:19168442 doi:10.1161/CIRCRESAHA.108.183905
↑ 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. Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway. Angew Chem Int Ed Engl. 2018 Dec 20. doi: 10.1002/anie.201810312. PMID:30569600 doi:http://dx.doi.org/10.1002/anie.201810312

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6i5h"

@@ Line 1: / Line 1: @@
 ==Crystal structure of CLK1 in complex with furanopyrimidin VN412==
-<StructureSection load='6i5h' size='340' side='right' caption='[[6i5h]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
+<StructureSection load='6i5h' size='340' side='right'caption='[[6i5h]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6i5h]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I5H FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6i5h]] 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=6I5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I5H FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H3N:5-(1-methylpyrazol-4-yl)-3-(3-phenoxyphenyl)furo[3,2-b]pyridine'>H3N</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]] 1.49&#8491;</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='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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H3N:5-(1-methylpyrazol-4-yl)-3-(3-phenoxyphenyl)furo[3,2-b]pyridine'>H3N</scene></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=6i5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i5h OCA], [http://pdbe.org/6i5h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i5h RCSB], [http://www.ebi.ac.uk/pdbsum/6i5h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i5h 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=6i5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i5h OCA], [https://pdbe.org/6i5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i5h RCSB], [https://www.ebi.ac.uk/pdbsum/6i5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i5h 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>
+[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 ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 6i5h" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Dual-specificity kinase]]
+[[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H]]
+[[Category: Large Structures]]
-[[Category: Bountra, C]]
+[[Category: Arrowsmith CH]]
-[[Category: Edwards, A M]]
+[[Category: Bountra C]]
-[[Category: Knapp, S]]
+[[Category: Edwards AM]]
-[[Category: Paruch, K]]
+[[Category: Knapp S]]
-[[Category: Structural genomic]]
+[[Category: Paruch K]]
-[[Category: Schroeder, M]]
+[[Category: Schroeder M]]
-[[Category: Dual specificity]]
-[[Category: Human]]
-[[Category: Inhibitor]]
-[[Category: Protein tyrosine kinase]]
-[[Category: Sgc]]
-[[Category: Splicing]]
-[[Category: Transferase]]

6i5h

From Proteopedia

Current revision

Crystal structure of CLK1 in complex with furanopyrimidin VN412

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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