6Q36

TEAD4(216-434) complexed with optimized peptide 9 and myristoate (covalently bound) at 2.01A resolution: Structure-based design of potent linear peptide inhibitors of the YAP-TEAD protein-protein interaction derived from the YAP omega-loop sequence

Summary for 6Q36

• Entry DOI: 10.2210/pdb6q36/pdb
• Descriptor: Transcriptional enhancer factor TEF-3, ACE-PRO-6CW-ARG-LEU-ARG-LYS-2JH-HYP-ASP-SER-PHE-ALN-LYS-GLU-PRO-NH2, MYRISTIC ACID, ... (5 entities in total)
• Functional Keywords: transcription factor, co-activator, transcription regulation, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 56145.94

Authors

Kallen, J. (deposition date: 2018-12-03, release date: 2019-07-03, Last modification date: 2024-01-24)

Primary citation

Furet, P.,Salem, B.,Mesrouze, Y.,Schmelzle, T.,Lewis, I.,Kallen, J.,Chene, P.
Structure-based design of potent linear peptide inhibitors of the YAP-TEAD protein-protein interaction derived from the YAP omega-loop sequence.
Bioorg.Med.Chem.Lett., 29:2316-2319, 2019

PubMed Abstract: The YAP-TEAD protein-protein interaction is a potential therapeutic target to treat cancers in which the Hippo signaling pathway is deregulated. However, the extremely large surface of interaction between the two proteins presents a formidable challenge for a small molecule interaction disrupter approach. We have accomplished progress towards showing the feasibility of this approach by the identification of a 15-mer peptide able to potently (nanomolar range) disrupt the YAP-TEAD interaction by targeting only one of the two important sites of interaction. This peptide, incorporating non-natural amino acids selected by structure-based design, is derived from the Ω-loop sequence 85-99 of YAP.

PubMed: 31235263
DOI: 10.1016/j.bmcl.2019.06.022

Experimental method

X-RAY DIFFRACTION (2.01 Å)