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7kx6
From Proteopedia
(Difference between revisions)
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==Crystal structure of DCLK1-KD in complex with XMD8-85== | ==Crystal structure of DCLK1-KD in complex with XMD8-85== | ||
| - | <StructureSection load='7kx6' size='340' side='right'caption='[[7kx6]]' scene=''> | + | <StructureSection load='7kx6' size='340' side='right'caption='[[7kx6]], [[Resolution|resolution]] 2.50Å' 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=7KX6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KX6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7kx6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KX6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KX6 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=7kx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kx6 OCA], [https://pdbe.org/7kx6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kx6 RCSB], [https://www.ebi.ac.uk/pdbsum/7kx6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kx6 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=X7Y:2-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}-5,11-dimethyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one'>X7Y</scene></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=7kx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kx6 OCA], [https://pdbe.org/7kx6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kx6 RCSB], [https://www.ebi.ac.uk/pdbsum/7kx6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kx6 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 == | ||
| + | Doublecortin-like kinase 1 (DCLK1) is an understudied bi-functional kinase with a proven role in tumour growth and development. However, the presence of tissue-specific spliced DCLK1 isoforms with distinct biological functions have challenged the development of effective strategies to understand the role of DCLK1 in oncogenesis. Recently, DCLK1-IN-1 was reported as a highly selective DCLK1 inhibitor, a powerful tool to dissect DCLK1 biological functions. Here, we report the crystal structures of DCLK1 kinase domain in complex with DCLK1-IN-1 and its precursors. Combined, our data rationalises the structure-activity relationship that informed the development of DCLK1-IN-1 and provides the basis for the high selectivity of DCLK1-IN-1, with DCLK1-IN-1 inducing a drastic conformational change of the ATP binding site. We demonstrate that DCLK1-IN-1 binds DCLK1 long isoforms but does not prevent DCLK1's Microtubule-Associated Protein (MAP) function. Together, our work provides an invaluable structural platform to further the design of isoform-specific DCLK1 modulators for therapeutic intervention. | ||
| + | |||
| + | Structural basis for small molecule targeting of Doublecortin Like Kinase 1 with DCLK1-IN-1.,Patel O, Roy MJ, Kropp A, Hardy JM, Dai W, Lucet IS Commun Biol. 2021 Sep 20;4(1):1105. doi: 10.1038/s42003-021-02631-y. PMID:34545159<ref>PMID:34545159</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7kx6" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Lucet I]] | + | [[Category: Non-specific serine/threonine protein kinase]] |
| - | [[Category: Patel O]] | + | [[Category: Lucet, I]] |
| + | [[Category: Patel, O]] | ||
| + | [[Category: Doublecortin-like]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 15:50, 27 October 2021
Crystal structure of DCLK1-KD in complex with XMD8-85
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