8R0Z

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

Summary for 8R0Z

• Entry DOI: 10.2210/pdb8r0z/pdb
• Descriptor: 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)
• Functional Keywords: protein complex, stabilization, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 29722.94

Authors

Centorrino, F.,Andlovic, B.,Ottmann, C. (deposition date: 2023-11-01, release date: 2024-09-04, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.2 Å)