5MXO

Crystal structure of 14-3-3sigma and a p53 C-terminal 12-mer synthetic phosphopeptide stabilized by Fusicoccin-A

5MXO の概要

• エントリーDOI: 10.2210/pdb5mxo/pdb
• 分子名称: 14-3-3 protein sigma, p53 C-terminal 12 amino acids, FUSICOCCIN, ... (6 entities in total)
• 機能のキーワード: 14-3-3 p53 fusicoccin antitumor protein, antitumor 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: 27758.95

構造登録者

Andrei, S.,Ottmann, C.,Leysen, S. (登録日: 2017-01-24, 公開日: 2017-11-08, 最終更新日: 2024-10-16)

主引用文献

Doveston, R.G.,Kuusk, A.,Andrei, S.A.,Leysen, S.,Cao, Q.,Castaldi, M.P.,Hendricks, A.,Brunsveld, L.,Chen, H.,Boyd, H.,Ottmann, C.
Small-molecule stabilization of the p53 - 14-3-3 protein-protein interaction.
FEBS Lett., 591:2449-2457, 2017

PubMed Abstract: 14-3-3 proteins are positive regulators of the tumor suppressor p53, the mutation of which is implicated in many human cancers. Current strategies for targeting of p53 involve restoration of wild-type function or inhibition of the interaction with MDM2, its key negative regulator. Despite the efficacy of these strategies, the alternate approach of stabilizing the interaction of p53 with positive regulators and, thus, enhancing tumor suppressor activity, has not been explored. Here, we report the first example of small-molecule stabilization of the 14-3-3 - p53 protein-protein interaction (PPI) and demonstrate the potential of this approach as a therapeutic modality. We also observed a disconnect between biophysical and crystallographic data in the presence of a stabilizing molecule, which is unusual in 14-3-3 PPIs.

PubMed: 28640363
DOI: 10.1002/1873-3468.12723

実験手法

X-RAY DIFFRACTION (1.2 Å)