5XJD
TEAD in complex with fragment
5XJD の概要
エントリーDOI | 10.2210/pdb5xjd/pdb |
分子名称 | Transcriptional enhancer factor TEF-3, (2S)-2-phenyl-2-pyrrol-1-yl-ethanoic acid (3 entities in total) |
機能のキーワード | transcription factor, transcription |
由来する生物種 | Mus musculus (Mouse) |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 51751.56 |
構造登録者 | Kaan, H.Y.K.,Sim, A.Y.L.,Tan, S.K.J.,Verma, C.,Song, H. (登録日: 2017-05-01, 公開日: 2018-01-24, 最終更新日: 2023-11-22) |
主引用文献 | 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 Cited by 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: 28570566DOI: 10.1371/journal.pone.0178381 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.22 Å) |
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