7f3g

Crystal structure of DCLK1 kinase domain in complex with ruxolitinib

spinqualitylabelsall models 7f3g, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7f3g is a 2 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 2.1Å Ligands: RXT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase 3D structures

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