5jzn
Crystal structure of DCLK1-KD in complex with NVP-TAE684
Structural highlights
FunctionDCLK1_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 PubMedDoublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that belongs to the family of microtubule-associated proteins. Originally identified for its role in neurogenesis, DCLK1 has recently been shown to regulate biological processes outside of the CNS. DCLK1 is among the 15 most common putative driver genes for gastric cancers and is highly mutated across various other human cancers. However, our present understanding of how DCLK1 dysfunction leads to tumorigenesis is limited. Here, we provide evidence that DCLK1 kinase activity negatively regulates microtubule polymerization. We present the crystal structure of the DCLK1 kinase domain at 1.7 A resolution, providing detailed insight into the ATP-binding site that will serve as a framework for future drug design. This structure also allowed for the mapping of cancer-causing mutations within the kinase domain, suggesting that a loss of kinase function may contribute to tumorigenesis. Biochemical and Structural Insights into Doublecortin-like Kinase Domain 1.,Patel O, Dai W, Mentzel M, Griffin MD, Serindoux J, Gay Y, Fischer S, Sterle S, Kropp A, Burns CJ, Ernst M, Buchert M, Lucet IS Structure. 2016 Sep 6;24(9):1550-61. doi: 10.1016/j.str.2016.07.008. Epub 2016, Aug 18. PMID:27545623[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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