5WNJ

Crystal structure of murine receptor-interacting protein kinase 4 (Ripk4) D143N in complex with lestaurtinib

5WNJ の概要

• エントリーDOI: 10.2210/pdb5wnj/pdb
• 関連するPDBエントリー: 5WNI 5WNK 5WNL 5WNM
• 分子名称: Receptor-interacting serine/threonine-protein kinase 4, Lestaurtinib, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: kinase, inhibitor, complex, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Cytoplasm: Q9ERK0
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39462.96

構造登録者

Huang, C.S.,Hymowitz, S.G. (登録日: 2017-08-01, 公開日: 2018-05-09, 最終更新日: 2024-05-22)

主引用文献

Huang, C.S.,Oberbeck, N.,Hsiao, Y.C.,Liu, P.,Johnson, A.R.,Dixit, V.M.,Hymowitz, S.G.
Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.
Structure, 26:767-, 2018

PubMed Abstract: Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease.

PubMed: 29706531
DOI: 10.1016/j.str.2018.04.002

実験手法

X-RAY DIFFRACTION (2.55 Å)