7ZHN

Crystal structure of TTBK1 in complex with AMG28

Summary for 7ZHN

• Entry DOI: 10.2210/pdb7zhn/pdb
• Descriptor: Tau-tubulin kinase 1, PHOSPHATE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: kinase, ttbk1, tau tubulin kinase 1, inhibitor complex, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 36314.81

Authors

Chaikuad, A.,Axtman, A.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2022-04-06, release date: 2023-04-19, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)