7PWT

Crystal structure of 14-3-3 sigma in complex with a C-terminal Estrogen Receptor alpha phosphopeptide, stabilised by pyrrolidone derivative 228

7PWT の概要

• エントリーDOI: 10.2210/pdb7pwt/pdb
• 分子名称: 14-3-3 protein sigma, C-terminus of Estrogen receptor alpha, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: nuclear receptor, phosphorylation, trafficking, ppi stabiliser, chaperone
• 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: 27854.44

構造登録者

Andrei, S.A.,Bosica, F.,O'Mahony, G.,Ottmann, C. (登録日: 2021-10-07, 公開日: 2022-12-21, 最終更新日: 2024-10-09)

主引用文献

Pallesen, J.S.,Munier, C.C.,Bosica, F.,Andrei, S.A.,Edman, K.,Gunnarsson, A.,La Sala, G.,Putra, O.D.,Srdanovic, S.,Wilson, A.J.,Wissler, L.,Ottmann, C.,Perry, M.W.D.,O'Mahony, G.
Designing Selective Drug-like Molecular Glues for the Glucocorticoid Receptor/14-3-3 Protein-Protein Interaction.
J.Med.Chem., 65:16818-16828, 2022

PubMed Abstract: The ubiquitously expressed glucocorticoid receptor (GR) is a nuclear receptor that controls a broad range of biological processes and is activated by steroidal glucocorticoids such as hydrocortisone or dexamethasone. Glucocorticoids are used to treat a wide variety of conditions, from inflammation to cancer but suffer from a range of side effects that motivate the search for safer GR modulators. GR is also regulated outside the steroid-binding site through protein-protein interactions (PPIs) with 14-3-3 adapter proteins. Manipulation of these PPIs will provide insights into noncanonical GR signaling as well as a new level of control over GR activity. We report the first molecular glues that selectively stabilize the 14-3-3/GR PPI using the related nuclear receptor estrogen receptor α (ERα) as a selectivity target to drive design. These 14-3-3/GR PPI stabilizers can be used to dissect noncanonical GR signaling and enable the development of novel atypical GR modulators.

PubMed: 36484727
DOI: 10.1021/acs.jmedchem.2c01635

実験手法

X-RAY DIFFRACTION (2.312 Å)