7kxw
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7kxw is ON HOLD Authors: Patel, O., Lucet, I. Description: Crystal structure of DCLK1-KD in complex with DCLK1-IN-1 [[Category: Unreleased Structur...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of DCLK1-KD in complex with DCLK1-IN-1== | |
| + | <StructureSection load='7kxw' size='340' side='right'caption='[[7kxw]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7kxw]] is a 2 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=7KXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KXW 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]] 3.002Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=XBD:2-[[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino]-11-methyl-5-[2,2,2-tris(fluoranyl)ethyl]pyrimido[4,5-b][1,4]benzodiazepin-6-one'>XBD</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=7kxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kxw OCA], [https://pdbe.org/7kxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kxw RCSB], [https://www.ebi.ac.uk/pdbsum/7kxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kxw ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <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> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 7kxw" style="background-color:#fffaf0;"></div> |
| - | [[Category: Lucet | + | |
| + | ==See Also== | ||
| + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lucet I]] | ||
| + | [[Category: Patel O]] | ||
Current revision
Crystal structure of DCLK1-KD in complex with DCLK1-IN-1
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