7OYJ

Crystal structure of hTEAD2 in complex with fragment at the interface 2

7OYJ の概要

• エントリーDOI: 10.2210/pdb7oyj/pdb
• 分子名称: Transcriptional enhancer factor TEF-4, PALMITIC ACID, 3-(1~{H}-pyrazol-5-yl)aniline, ... (4 entities in total)
• 機能のキーワード: tead, fragment, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55650.23

構造登録者

Guichou, J.F.,Gelin, M.,Allemand, F. (登録日: 2021-06-24, 公開日: 2022-05-25, 最終更新日: 2024-01-31)

主引用文献

Liberelle, M.,Toulotte, F.,Renault, N.,Gelin, M.,Allemand, F.,Melnyk, P.,Guichou, J.F.,Cotelle, P.
Toward the Design of Ligands Selective for the C-Terminal Domain of TEADs.
J.Med.Chem., 65:5926-5940, 2022

PubMed Abstract: The Hippo signaling pathway plays a fundamental role in the control of organ growth, cell proliferation, and stem cell characters. TEADs are the main transcriptional output regulators of the Hippo signaling pathway and bind to YAP and TAZ co-activators. TEAD1-4 are expressed differently, depending on the tissue and developmental level, and can be overexpressed in certain pathologies. TEAD ligands mainly target the internal pocket of the C-terminal domain of TEAD, and the first ligands selective for TEAD1 and TEAD3 have been recently reported. In this paper, we focus on the topographic homology of the TEAD C-terminal domain both externally and in the internal pocket to highlight the possibility of rationally designing ligands selective for one of the TEAD family members. We identified a novel TEAD2-specific pocket and reported its first ligand. Finally, AlphaFold2 models of full-length TEADs suggest TEAD autoregulation and emphasize the importance of the interface 2.

PubMed: 35389210
DOI: 10.1021/acs.jmedchem.2c00075

実験手法

X-RAY DIFFRACTION (1.91 Å)