7BA3

Cys-42-tethered stabilizer 6 of 14-3-3(sigma)/ERa PPI

7BA3 の概要

• エントリーDOI: 10.2210/pdb7ba3/pdb
• 分子名称: 14-3-3 protein sigma, Estrogen receptor, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: protein-protein interaction, stabilizer, hub protein, transcription factor, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27804.90

構造登録者

Sijbesma, E.,Ottmann, C. (登録日: 2020-12-15, 公開日: 2021-07-07, 最終更新日: 2024-11-13)

主引用文献

Sijbesma, E.,Hallenbeck, K.K.,Andrei, S.A.,Rust, R.R.,Adriaans, J.M.C.,Brunsveld, L.,Arkin, M.R.,Ottmann, C.
Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers.
Acs Med.Chem.Lett., 12:976-982, 2021

PubMed Abstract: The systematic discovery of functional fragments binding to the composite interface of protein complexes is a first critical step for the development of orthosteric stabilizers of protein-protein interactions (PPIs). We have previously shown that disulfide trapping successfully yielded covalent stabilizers for the PPI of 14-3-3 with the estrogen receptor ERα. Here we provide an assessment of the composite PPI target pocket and the molecular characteristics of various fragments binding to a specific subpocket. Evaluating structure-activity relationships highlights the basic principles for PPI stabilization by these covalent fragments that engage a relatively large and exposed binding pocket at the protein/peptide interface with a "molecular glue" mode of action.

PubMed: 34136078
DOI: 10.1021/acsmedchemlett.1c00088

実験手法

X-RAY DIFFRACTION (1.4 Å)