4G3D

Crystal structure of human NF-kappaB inducing kinase (NIK)

4G3D の概要

• エントリーDOI: 10.2210/pdb4g3d/pdb
• 関連するPDBエントリー: 4G3C 4G3E 4G3F 4G3G
• 分子名称: NF-kappa-beta-inducing kinase, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: non-rd kinase, protein serine/threonine kinase, nf-kappab, map3k14, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q99558
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 162922.49

構造登録者

Hymowitz, S.G.,de Leon-Boenig, G. (登録日: 2012-07-13, 公開日: 2012-08-15, 最終更新日: 2024-02-28)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.9 Å)