7f3g
From Proteopedia
(Difference between revisions)
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==Crystal structure of DCLK1 kinase domain in complex with ruxolitinib== | ==Crystal structure of DCLK1 kinase domain in complex with ruxolitinib== | ||
| - | <StructureSection load='7f3g' size='340' side='right'caption='[[7f3g]]' scene=''> | + | <StructureSection load='7f3g' size='340' side='right'caption='[[7f3g]], [[Resolution|resolution]] 2.10Å' 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=7F3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F3G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7f3g]] is a 2 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=7F3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F3G FirstGlance]. <br> |
| - | </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=7f3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f3g OCA], [https://pdbe.org/7f3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f3g RCSB], [https://www.ebi.ac.uk/pdbsum/7f3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f3g ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RXT:(3R)-3-CYCLOPENTYL-3-[4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-1H-PYRAZOL-1-YL]PROPANENITRILE'>RXT</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCLK1, DCAMKL1, DCDC3A, KIAA0369 ([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/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=7f3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f3g OCA], [https://pdbe.org/7f3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f3g RCSB], [https://www.ebi.ac.uk/pdbsum/7f3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f3g ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/DCLK1_HUMAN DCLK1_HUMAN]] Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Given the functional attributes of Doublecortin-like kinase 1 (DCLK1) in tumor growth, invasion, metastasis, cell motility, and tumor stemness, it is emerging as a therapeutic target in gastrointestinal cancers. Although a series of specific or nonspecific ATP-competitive inhibitors were identified against DCLK1, different types of scaffolds that can be utilized for the development of highly selective inhibitors or structural understanding of binding specificities of the compounds remain limited. Here, we present our work to repurpose a Janus kinase 1 inhibitor, ruxolitinib as a DCLK1 inhibitor, showing micromolar binding affinity and inhibitory activity. Furthermore, to gain an insight into its interaction mode with DCLK1, a crystal structure of the ruxolitinib-complexed DCLK1 has been determined and analyzed. Ruxolitinib as a nonspecific DCLK1 inhibitor characterized in this work is anticipated to provide a starting point for the structure-guided discovery of selective DCLK1 inhibitors. | ||
| + | |||
| + | Structural Basis of Inhibition of DCLK1 by Ruxolitinib.,Jang DM, Lim HJ, Hahn H, Lee Y, Kim HK, Kim HS Int J Mol Sci. 2021 Aug 6;22(16). pii: ijms22168488. doi: 10.3390/ijms22168488. PMID:34445192<ref>PMID:34445192</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7f3g" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Jang | + | [[Category: Non-specific serine/threonine protein kinase]] |
| - | [[Category: Kim | + | [[Category: Jang, D M]] |
| - | [[Category: Lim | + | [[Category: Kim, H S]] |
| + | [[Category: Lim, H J]] | ||
| + | [[Category: Doublecortin-like kinase 1]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Kinase domain]] | ||
| + | [[Category: Ruxolitinib]] | ||
| + | [[Category: Signaling protein]] | ||
Revision as of 11:49, 27 April 2022
Crystal structure of DCLK1 kinase domain in complex with ruxolitinib
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