5HF3

Crystal structure of C-terminal modified Tau peptide-hybrid 201D with 14-3-3sigma

「4Y3B」から置き換えられました

5HF3 の概要

• エントリーDOI: 10.2210/pdb5hf3/pdb
• 関連するPDBエントリー: 4Y3B
• 分子名称: 14-3-3 protein sigma, modified Tau peptide (3 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm: P31947
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27656.14

構造登録者

Bartel, M.,Milroy, L.G.,Brunsveld, L.,Ottmann, C. (登録日: 2016-01-06, 公開日: 2016-01-27, 最終更新日: 2025-09-17)

主引用文献

Milroy, L.G.,Bartel, M.,Henen, M.A.,Leysen, S.,Adriaans, J.M.,Brunsveld, L.,Landrieu, I.,Ottmann, C.
Stabilizer-Guided Inhibition of Protein-Protein Interactions.
Angew.Chem.Int.Ed.Engl., 54:15720-15724, 2015

PubMed Abstract: The discovery of novel protein-protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein-stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X-ray crystallographic data from both stabilizer and inhibitor co-crystal complexes of the adapter protein 14-3-3 to characterize, down to the atomic scale, inhibitors of the 14-3-3/Tau PPI, a potential drug target to treat Alzheimer's disease. The most potent compound notably inhibited the binding of phosphorylated full-length Tau to 14-3-3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer-protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14-3-3 and other PPIs.

PubMed: 26537010
DOI: 10.1002/anie.201507976

実験手法

X-RAY DIFFRACTION (1.8 Å)