5XJD

TEAD in complex with fragment

Summary for 5XJD

• Entry DOI: 10.2210/pdb5xjd/pdb
• Descriptor: Transcriptional enhancer factor TEF-3, (2S)-2-phenyl-2-pyrrol-1-yl-ethanoic acid (3 entities in total)
• Functional Keywords: transcription factor, transcription
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 51751.56

Authors

Kaan, H.Y.K.,Sim, A.Y.L.,Tan, S.K.J.,Verma, C.,Song, H. (deposition date: 2017-05-01, release date: 2018-01-24, Last modification date: 2023-11-22)

Primary citation

Kaan, H.Y.K.,Sim, A.Y.L.,Tan, S.K.J.,Verma, C.,Song, H.
Targeting YAP/TAZ-TEAD protein-protein interactions using fragment-based and computational modeling approaches.
PLoS ONE, 12:e0178381-e0178381, 2017

PubMed Abstract: The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment. We confirmed its binding at the YAP/TAZ-TEAD interface by X-ray crystallography, and showed that it occupies the same hydrophobic pocket as a conserved phenylalanine of YAP/TAZ. This hit fragment serves as a scaffold for the development of compounds that have the potential to disrupt YAP/TAZ-TEAD interactions. Structure-activity relationship studies and computational modeling were also carried out to identify more potent compounds that may bind at this validated druggable binding site.

PubMed: 28570566
DOI: 10.1371/journal.pone.0178381

Experimental method

X-RAY DIFFRACTION (2.22 Å)