5IH5

Human Casein Kinase 1 isoform delta (kinase domain) in complex with Epiblastin A

5IH5 の概要

• エントリーDOI: 10.2210/pdb5ih5/pdb
• 分子名称: Casein kinase I isoform delta, ZINC ION, 6-(3-chlorophenyl)pteridine-2,4,7-triamine, ... (6 entities in total)
• 機能のキーワード: kinase domain, stem cell reprogramming, kinase inhibitor complex, transferase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P48730
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34901.86

構造登録者

Ursu, A.,Illich, D.J.,Takemoto, Y.,Porfetye, A.T.,Zhang, M.,Brockmeyer, A.,Janning, P.,Watanabe, N.,Osada, H.,Vetter, I.R.,Ziegler, S.,Schoeler, H.R.,Waldmann, H. (登録日: 2016-02-29, 公開日: 2016-04-13, 最終更新日: 2024-01-10)

主引用文献

Ursu, A.,Illich, D.J.,Takemoto, Y.,Porfetye, A.T.,Zhang, M.,Brockmeyer, A.,Janning, P.,Watanabe, N.,Osada, H.,Vetter, I.R.,Ziegler, S.,Scholer, H.R.,Waldmann, H.
Epiblastin A Induces Reprogramming of Epiblast Stem Cells Into Embryonic Stem Cells by Inhibition of Casein Kinase 1.
Cell Chem Biol, 23:494-507, 2016

PubMed Abstract: The discovery of novel small molecules that induce stem cell reprogramming and give efficient access to pluripotent stem cells is of major importance for potential therapeutic applications and may reveal novel insights into the factors controlling pluripotency. Chemical reprogramming of mouse epiblast stem cells (EpiSCs) into cells corresponding to embryonic stem cells (cESCs) is an inefficient process. In order to identify small molecules that promote this cellular transition, we analyzed the LOPAC library in a phenotypic screen monitoring Oct4-GFP expression and identified triamterene (TR) as initial hit. Synthesis of a TR-derived compound collection and investigation for reprogramming of EpiSCs into cESCs identified casein kinases 1 (CK1) α/δ/ɛ as responsible cellular targets of TR and unraveled the structural parameters that determine reprogramming. Delineation of a structure-activity relationship led to the development of Epiblastin A, which engages CK1 isoenzymes in cell lysate and induces efficient conversion of EpiSCs into cESCs.

PubMed: 27049670
DOI: 10.1016/j.chembiol.2016.02.015

実験手法

X-RAY DIFFRACTION (2.25 Å)