6bsd: Difference between revisions
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==DDR1 bound to Dasatinib== | |||
<StructureSection load='6bsd' size='340' side='right'caption='[[6bsd]], [[Resolution|resolution]] 2.61Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6bsd]] 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=6BSD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BSD 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]] 2.606Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1N1:N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE'>1N1</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=6bsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bsd OCA], [https://pdbe.org/6bsd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bsd RCSB], [https://www.ebi.ac.uk/pdbsum/6bsd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bsd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DDR1_HUMAN DDR1_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
ATP-competitive kinase inhibitors often bind several kinases due to the high conservation of the ATP binding pocket. Through clustering analysis of a large kinome profiling dataset, we found a cluster of eight promiscuous kinases that on average bind more than five times more kinase inhibitors than the other 398 kinases in the dataset. To understand the structural basis of promiscuous inhibitor binding, we determined the co-crystal structure of the receptor tyrosine kinase DDR1 with the type I inhibitors dasatinib and VX-680. Surprisingly, we find that DDR1 binds these type I inhibitors in an inactive conformation typically reserved for type II inhibitors. Our computational and biochemical studies show that DDR1 is unusually stable in this inactive conformation, giving a mechanistic explanation for inhibitor promiscuity. This phenotypic clustering analysis provides a strategy to obtain functional insights not available by sequence comparison alone. | |||
What Makes a Kinase Promiscuous for Inhibitors?,Hanson SM, Georghiou G, Thakur MK, Miller WT, Rest JS, Chodera JD, Seeliger MA Cell Chem Biol. 2019 Mar 21;26(3):390-399.e5. doi:, 10.1016/j.chembiol.2018.11.005. Epub 2019 Jan 3. PMID:30612951<ref>PMID:30612951</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6bsd" style="background-color:#fffaf0;"></div> | ||
[[Category: Georghiou | |||
==See Also== | |||
*[[Epithelial discoidin domain-containing receptor|Epithelial discoidin domain-containing receptor]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Georghiou G]] | |||
[[Category: Seeliger MA]] | |||
