6RX2

Fragment AZ-005 binding at the p53pT387/14-3-3 sigma interface

6RX2 の概要

• エントリーDOI: 10.2210/pdb6rx2/pdb
• 分子名称: 14-3-3 protein sigma, Cellular tumor antigen p53, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: protein protein interaction, fragment soaking, stabilization, 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: 2
• 化学式量合計: 30037.38

構造登録者

Leysen, S.,Guillory, X.,Wolter, M.,Genet, S.,Somsen, B.,Patel, J.,Castaldi, P.,Ottmann, C. (登録日: 2019-06-07, 公開日: 2020-06-17, 最終更新日: 2024-11-06)

主引用文献

Guillory, X.,Wolter, M.,Leysen, S.,Neves, J.F.,Kuusk, A.,Genet, S.,Somsen, B.,Morrow, J.K.,Rivers, E.,van Beek, L.,Patel, J.,Goodnow, R.,Schoenherr, H.,Fuller, N.,Cao, Q.,Doveston, R.G.,Brunsveld, L.,Arkin, M.R.,Castaldi, P.,Boyd, H.,Landrieu, I.,Chen, H.,Ottmann, C.
Fragment-based Differential Targeting of PPI Stabilizer Interfaces.
J.Med.Chem., 63:6694-6707, 2020

PubMed Abstract: Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragment-based approach can be used to identify chemical starting points for the development of small-molecule stabilizers that differentiate between two different PPI interfaces of the adapter protein 14-3-3. The fragments discriminately bind to the interface of 14-3-3 with the recognition motif of either the tumor suppressor protein p53 or the oncogenic transcription factor TAZ. This X-ray crystallography driven study shows that the rim of the interface of individual 14-3-3 complexes can be targeted in a differential manner with fragments that represent promising starting points for the development of specific 14-3-3 PPI stabilizers.

PubMed: 32501690
DOI: 10.1021/acs.jmedchem.9b01942

実験手法

X-RAY DIFFRACTION (1.82 Å)