6Q2X

TEAD4 (216-434) COMPLEXED WITH YAP PEPTIDE (60-100) AND MYRISTOATE (COVALENTLY BOUND) AT 2.1A (P41212 CRYSTAL FORM)

Summary for 6Q2X

• Entry DOI: 10.2210/pdb6q2x/pdb
• Descriptor: Transcriptional enhancer factor TEF-3, Transcriptional coactivator YAP1, GLYCEROL, ... (5 entities in total)
• Functional Keywords: other, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 30568.61

Authors

Kallen, J. (deposition date: 2018-12-03, release date: 2019-07-03, Last modification date: 2024-11-13)

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 (2.1 Å)