6myn | pdb_00006myn

Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to inhibitor R7

spinqualitylabelsall models 6myn, resolution 2.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6myn is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: K6Y, SO4 Related: 4g3c Gene: Map3k14, Nik (LK3 transgenic mice) Activity: Mitogen-activated protein kinase kinase kinase, with EC number 2.7.11.25 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [M3K14_MOUSE] Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner. Publication Abstract from PubMed We previously disclosed a series of type I 1/2 inhibitors of NF-kappaB inducing kinase (NIK). Inhibition of NIK by these compounds was found to be strongly dependent on the inclusion and absolute stereochemistry of a propargyl tertiary alcohol as it forms critical hydrogen bonds (H-bonds) with NIK. We report that inhibition of protein kinase D1 (PKD1) by this class of compounds is not dependent on H-bond interactions of this tertiary alcohol. This feature was leveraged in the design of highly selective inhibitors of PKD1 that no longer inhibit NIK. A structure-based hypothesis based on the position and flexibility of the alpha-C-helix of PKD1 vs NIK is presented. Structure Based Design of Potent Selective Inhibitors of Protein Kinase D1 (PKD1).,Feng JA, Lee P, Alaoui MH, Barrett K, Castanedo G, Godemann R, McEwan P, Wang X, Wu P, Zhang Y, Harris SF, Staben ST ACS Med Chem Lett. 2019 Jul 24;10(9):1260-1265. doi:, 10.1021/acsmedchemlett.8b00658. eCollection 2019 Sep 12. PMID:31531194 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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