6bsd

DDR1 bound to Dasatinib

spinqualitylabelsall models 6bsd, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bsd 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 2.606Å Ligands: 1N1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DDR1_HUMAN 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Epithelial discoidin domain-containing receptor

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