8R07

C-terminal Rel-homology Domain of NFAT1

8R07 の概要

• エントリーDOI: 10.2210/pdb8r07/pdb
• 分子名称: Nuclear factor of activated T-cells, cytoplasmic 2 (2 entities in total)
• 機能のキーワード: nfat1, transcription factor, 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: 24551.73

構造登録者

Zak, K.M.,Boettcher, J. (登録日: 2023-10-30, 公開日: 2024-03-06, 最終更新日: 2024-06-12)

主引用文献

Bottcher, J.,Fuchs, J.E.,Mayer, M.,Kahmann, J.,Zak, K.M.,Wunberg, T.,Woehrle, S.,Kessler, D.
Ligandability assessment of the C-terminal Rel-homology domain of NFAT1.
Arch Pharm, 357:e2300649-e2300649, 2024

PubMed Abstract: Transcription factors are generally considered challenging, if not "undruggable", targets but they promise new therapeutic options due to their fundamental involvement in many diseases. In this study, we aim to assess the ligandability of the C-terminal Rel-homology domain of nuclear factor of activated T cells 1 (NFAT1), a TF implicated in T-cell regulation. Using a combination of experimental and computational approaches, we demonstrate that small molecule fragments can indeed bind to this protein domain. The newly identified binder is the first small molecule binder to NFAT1 validated with biophysical methods and an elucidated binding mode by X-ray crystallography. The reported eutomer/distomer pair provides a strong basis for potential exploration of higher potency binders on the path toward degrader or glue modalities.

PubMed: 38396281
DOI: 10.1002/ardp.202300649

実験手法

X-RAY DIFFRACTION (1.74 Å)