4AAA

Crystal structure of the human CDKL2 kinase domain

4AAA の概要

• エントリーDOI: 10.2210/pdb4aaa/pdb
• 分子名称: CYCLIN-DEPENDENT KINASE-LIKE 2, 5-AMINO-3-{[4-(AMINOSULFONYL)PHENYL]AMINO}-N-(2,6-DIFLUOROPHENYL)-1H-1,2,4-TRIAZOLE-1-CARBOTHIOAMIDE, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: transferase, phospho-mimetic
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm : Q92772
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39188.30

構造登録者

Canning, P.,Vollmar, M.,Cooper, C.D.O.,Mahajan, P.,Daga, N.,Berridge, G.,Burgess-Brown, N.,Muniz, J.R.C.,Krojer, T.,von Delft, F.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Bullock, A. (登録日: 2011-11-30, 公開日: 2011-12-21, 最終更新日: 2023-12-20)

主引用文献

Canning, P.,Park, K.,Goncalves, J.,Li, C.,Howard, C.J.,Sharpe, T.D.,Holt, L.J.,Pelletier, L.,Bullock, A.N.,Leroux, M.R.
CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.
Cell Rep, 22:885-894, 2018

PubMed Abstract: Various kinases, including a cyclin-dependent kinase (CDK) family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL) proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs), including an unusual ?J helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1-4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and ?J helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy.

PubMed: 29420175
DOI: 10.1016/j.celrep.2017.12.083

実験手法

X-RAY DIFFRACTION (1.53 Å)