4g3e

Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to a 6-alkynylindoline (cmp1)

spinqualitylabelsall models 4g3e, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4g3e 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: 0WC, SO4 Related: 4g3c, 4g3d, 4g3f, 4g3g Gene: Map3k14, NF-kappaB inducing kinase, 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 The NF-kappaB inducing kinase (NIK) regulates the non-canonical NF-kappaB pathway downstream of important clinical targets including BAFF, RANKL, and LTbeta. Despite numerous genetic studies associating dysregulation of this pathway with autoimmune diseases and hematological cancers, detailed molecular characterization of this central signaling node has been lacking. We undertook a systematic cloning and expression effort to generate soluble, well-behaved proteins encompassing the kinase domains of human and murine NIK. Structures of the apo NIK kinase domain from both species reveal an active-like conformation in the absence of phosphorylation. ATP consumption and peptide phosphorylation assays confirm that phosphorylation of NIK does not increase enzymatic activity. Structures of murine NIK bound to inhibitors possessing two different chemotypes reveal conformational flexibility in the gatekeeper residue controlling access to a hydrophobic pocket. Finally, a single amino acid difference affects the ability of some inhibitors to bind murine and human NIK with the same affinity. The crystal structure of the catalytic domain of the NF-kappaB inducing kinase reveals a narrow but flexible active site.,de Leon-Boenig G, Bowman KK, Feng JA, Crawford T, Everett C, Franke Y, Oh A, Stanley M, Staben ST, Starovasnik MA, Wallweber HJ, Wu J, Wu LC, Johnson AR, Hymowitz SG Structure. 2012 Oct 10;20(10):1704-14. doi: 10.1016/j.str.2012.07.013. Epub 2012 , Aug 23. PMID:22921830 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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