5MOC

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

Summary for 5MOC

• Entry DOI: 10.2210/pdb5moc/pdb
• Descriptor: 14-3-3 protein sigma, p53 C-terminal domain, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: 14-3-3 p53 c-terminus, antitumor protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 28052.19

Authors

Andrei, S.,Ottmann, C.,Leysen, S. (deposition date: 2016-12-14, release date: 2017-10-04, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)