6QMS

NF-YB/C Heterodimer in Complex with NF-YA-derived Peptide Stabilized with C11-Hydrocarbon Linker

6QMS の概要

• エントリーDOI: 10.2210/pdb6qms/pdb
• 分子名称: Nuclear transcription factor Y subunit alpha, Nuclear transcription factor Y subunit beta, Nuclear transcription factor Y subunit gamma, ... (4 entities in total)
• 機能のキーワード: stapled peptide histone fold transcription factor, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 24570.77

構造登録者

Kiehstaller, S.,Jeganathan, S.,Pearce, N.M.,Wendt, M.,Grossmann, T.N.,Hennig, S. (登録日: 2019-02-08, 公開日: 2019-10-02, 最終更新日: 2024-11-06)

主引用文献

Jeganathan, S.,Wendt, M.,Kiehstaller, S.,Brancaccio, D.,Kuepper, A.,Pospiech, N.,Carotenuto, A.,Novellino, E.,Hennig, S.,Grossmann, T.N.
Constrained Peptides with Fine-Tuned Flexibility Inhibit NF-Y Transcription Factor Assembly.
Angew.Chem.Int.Ed.Engl., 58:17351-17358, 2019

PubMed Abstract: Protein complex formation depends on the interplay between preorganization and flexibility of the binding epitopes involved. The design of epitope mimetics typically focuses on stabilizing a particular bioactive conformation, often without considering conformational dynamics, which limits the potential of peptidomimetics against challenging targets such as transcription factors. We developed a peptide-derived inhibitor of the NF-Y transcription factor by first constraining the conformation of an epitope through hydrocarbon stapling and then fine-tuning its flexibility. In the initial set of constrained peptides, a single non-interacting α-methyl group was observed to have a detrimental effect on complex stability. Biophysical characterization revealed how this methyl group affects the conformation of the peptide in its bound state. Adaption of the methylation pattern resulted in a peptide that inhibits transcription factor assembly and subsequent recruitment to the target DNA.

PubMed: 31539186
DOI: 10.1002/anie.201907901

実験手法

X-RAY DIFFRACTION (1.8 Å)