6Y7T

Engineered conjugation of lysine-specific molecular tweezers with ExoS derived peptidic inhibitor enhance affinity towards target protein 14-3-3 through ditopic binding

6Y7T の概要

• エントリーDOI: 10.2210/pdb6y7t/pdb
• 分子名称: 14-3-3 protein sigma, Exoenzyme S, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: protein-protein interactions, supramolecular ligands, molecular tweezers, protein recognition, hybrid ligands, peptide binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 117195.25

構造登録者

Guillory, X.,Ottmann, C. (登録日: 2020-03-02, 公開日: 2021-03-31, 最終更新日: 2026-01-21)

主引用文献

Guillory, X.,Hadrovic, I.,de Vink, P.J.,Sowislok, A.,Brunsveld, L.,Schrader, T.,Ottmann, C.
Supramolecular Enhancement of a Natural 14-3-3 Protein Ligand.
J.Am.Chem.Soc., 143:13495-13500, 2021

PubMed Abstract: Rational design of protein-protein interaction (PPI) inhibitors is challenging. Connecting a general supramolecular protein binder with a specific peptidic ligand provides a novel conceptual approach. Thus, lysine-specific molecular tweezers were conjugated to a peptide-based 14-3-3 ligand and produced a strong PPI inhibitor with 100-fold elevated protein affinity. X-ray crystal structure elucidation of this supramolecular directed assembly provides unique molecular insight into the binding mode and fully aligns with Molecular Dynamics (MD) simulations. This new supramolecular chemical biology concept opens the path to novel chemical tools for studying PPIs.

PubMed: 34427424
DOI: 10.1021/jacs.1c07095

実験手法

X-RAY DIFFRACTION (2.5 Å)