8R0Z

14-3-3 sigma in complex with TAZ peptide and stabilizing fragment TCF199

8R0Z の概要

• エントリーDOI: 10.2210/pdb8r0z/pdb
• 分子名称: 14-3-3 protein sigma, WW domain-containing transcription regulator protein 1, [(4aR,8aR)-2,3,4,5,6,7,8,8a-octahydro-1H-quinolin-4a-yl]methyl N-phenylcarbamate, ... (5 entities in total)
• 機能のキーワード: protein complex, stabilization, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29722.94

構造登録者

Centorrino, F.,Andlovic, B.,Ottmann, C. (登録日: 2023-11-01, 公開日: 2024-09-04, 最終更新日: 2024-11-06)

主引用文献

Andlovic, B.,Valenti, D.,Centorrino, F.,Picarazzi, F.,Hristeva, S.,Hiltmann, M.,Wolf, A.,Cantrelle, F.X.,Mori, M.,Landrieu, I.,Levy, L.M.,Klebl, B.,Tzalis, D.,Genski, T.,Eickhoff, J.,Ottmann, C.
Fragment-Based Interrogation of the 14-3-3/TAZ Protein-Protein Interaction.
Biochemistry, 63:2196-2206, 2024

PubMed Abstract: The identification of chemical starting points for the development of molecular glues is challenging. Here, we employed fragment screening and identified an allosteric stabilizer of the complex between 14-3-3 and a TAZ-derived peptide. The fragment binds preferentially to the 14-3-3/TAZ peptide complex and shows moderate stabilization in differential scanning fluorimetry and microscale thermophoresis. The binding site of the fragment was predicted by molecular dynamics calculations to be distant from the 14-3-3/TAZ peptide interface, located between helices 8 and 9 of the 14-3-3 protein. This site was confirmed by nuclear magnetic resonance and X-ray protein crystallography, revealing the first example of an allosteric stabilizer for 14-3-3 protein-protein interactions.

PubMed: 39172504
DOI: 10.1021/acs.biochem.4c00248

実験手法

X-RAY DIFFRACTION (1.2 Å)