7ZHO

Crystal structure of TTBK1 in complex with compound 3 (7-001)

7ZHO の概要

• エントリーDOI: 10.2210/pdb7zho/pdb
• 分子名称: Tau-tubulin kinase 1, PHOSPHATE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: kinase, ttbk1, tau tubulin kinase 1, inhibitor complex, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36150.61

構造登録者

Chaikuad, A.,Axtman, A.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2022-04-06, 公開日: 2023-04-19, 最終更新日: 2024-02-07)

主引用文献

Bashore, F.M.,Marquez, A.B.,Chaikuad, A.,Howell, S.,Dunn, A.S.,Beltran, A.A.,Smith, J.L.,Drewry, D.H.,Beltran, A.S.,Axtman, A.D.
Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.
Sci Rep, 13:6118-6118, 2023

PubMed Abstract: Tau tubulin kinase 1 and 2 (TTBK1/2) are highly homologous kinases that are expressed and mediate disease-relevant pathways predominantly in the brain. Distinct roles for TTBK1 and TTBK2 have been delineated. While efforts have been devoted to characterizing the impact of TTBK1 inhibition in diseases like Alzheimer's disease and amyotrophic lateral sclerosis, TTBK2 inhibition has been less explored. TTBK2 serves a critical function during cilia assembly. Given the biological importance of these kinases, we designed a targeted library from which we identified several chemical tools that engage TTBK1 and TTBK2 in cells and inhibit their downstream signaling. Indolyl pyrimidinamine 10 significantly reduced the expression of primary cilia on the surface of human induced pluripotent stem cells (iPSCs). Furthermore, analog 10 phenocopies TTBK2 knockout in iPSCs, confirming a role for TTBK2 in ciliogenesis.

PubMed: 37059819
DOI: 10.1038/s41598-023-32854-4

実験手法

X-RAY DIFFRACTION (2.08 Å)