4N84

Crystal structure of 14-3-3zeta in complex with a 12-carbon-linker cyclic peptide derived from ExoS

4N84 の概要

• エントリーDOI: 10.2210/pdb4n84/pdb
• 関連するPDBエントリー: 3CH8 3NKX 4IEA 4IHL 4N7G 4N7Y
• 分子名称: 14-3-3 protein zeta/delta, Exoenzyme S (3 entities in total)
• 機能のキーワード: 14-3-3, adaptor protein, protein-protein interaction, cross-link, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P63104
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 54748.01

構造登録者

Bier, D.,Glas, A.,Hahne, G.,Grossmann, T.,Ottmann, C. (登録日: 2013-10-17, 公開日: 2014-02-19, 最終更新日: 2024-11-06)

主引用文献

Glas, A.,Bier, D.,Hahne, G.,Rademacher, C.,Ottmann, C.,Grossmann, T.N.
Constrained peptides with target-adapted cross-links as inhibitors of a pathogenic protein-protein interaction.
Angew.Chem.Int.Ed.Engl., 53:2489-2493, 2014

PubMed Abstract: Bioactive conformations of peptides can be stabilized by macrocyclization, resulting in increased target affinity and activity. Such macrocyclic peptides proved useful as modulators of biological functions, in particular as inhibitors of protein-protein interactions (PPI). However, most peptide-derived PPI inhibitors involve stabilized α-helices, leaving a large number of secondary structures unaddressed. Herein, we present a rational approach towards stabilization of an irregular peptide structure, using hydrophobic cross-links that replace residues crucially involved in target binding. The molecular basis of this interaction was elucidated by X-ray crystallography and isothermal titration calorimetry. The resulting cross-linked peptides inhibit the interaction between human adaptor protein 14-3-3 and virulence factor exoenzyme S. Taking into consideration that irregular peptide structures participate widely in PPIs, this approach provides access to novel peptide-derived inhibitors.

PubMed: 24504455
DOI: 10.1002/anie.201310082

実験手法

X-RAY DIFFRACTION (2.5 Å)