4G3C

Crystal structure of apo murine Nf-kappaB inducing kinase (NIK)

Summary for 4G3C

• Entry DOI: 10.2210/pdb4g3c/pdb
• Related: 4G3D 4G3E 4G3F 4G3G
• Descriptor: NF-kappa-beta-inducing kinase, SULFATE ION (3 entities in total)
• Functional Keywords: non-rd kinase, protein serine/threonine kinase, nf-kappab, map3k14, transferase
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm: Q9WUL6
• Total number of polymer chains: 2
• Total formula weight: 78179.74

Authors

Hymowitz, S.G.,de Leon-Boenig, G. (deposition date: 2012-07-13, release date: 2012-08-08, Last modification date: 2024-04-03)

Primary citation

de Leon-Boenig, G.,Bowman, K.K.,Feng, J.A.,Crawford, T.,Everett, C.,Franke, Y.,Oh, A.,Stanley, M.,Staben, S.T.,Starovasnik, M.A.,Wallweber, H.J.,Wu, J.,Wu, L.C.,Johnson, A.R.,Hymowitz, S.G.
The crystal structure of the catalytic domain of the NF-kappaB inducing kinase reveals a narrow but flexible active site.
Structure, 20:1704-1714, 2012

PubMed Abstract: The NF-κB inducing kinase (NIK) regulates the non-canonical NF-κB pathway downstream of important clinical targets including BAFF, RANKL, and LTβ. 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.

PubMed: 22921830
DOI: 10.1016/j.str.2012.07.013

Experimental method

X-RAY DIFFRACTION (2.15 Å)