4W9P

The Fk1 domain of FKBP51 in complex with (1S,5S,6R)-10-[(3,5-dichlorophenyl)sulfonyl]-5-[(1S)-1,2-dihydroxyethyl]-3-[2-(3,4-dimethoxyphenoxy)ethyl]-3,10-diazabicyclo[4.3.1]decan-2-one

4W9P の概要

• エントリーDOI: 10.2210/pdb4w9p/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP5, (1S,5S,6R)-10-[(3,5-dichlorophenyl)sulfonyl]-5-[(1S)-1,2-dihydroxyethyl]-3-[2-(3,4-dimethoxyphenoxy)ethyl]-3,10-diazabicyclo[4.3.1]decan-2-one, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: fk-506 binding domain, hsp90 cochaperone, immunophiline, peptidyl-prolyl isomerase, ligand selectivity, isomerase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: Q13451
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29377.27

構造登録者

Pomplun, S.,Wang, Y.,Kirschner, K.,Kozany, C.,Bracher, A.,Hausch, F. (登録日: 2014-08-27, 公開日: 2014-12-03, 最終更新日: 2024-01-10)

主引用文献

Pomplun, S.,Wang, Y.,Kirschner, A.,Kozany, C.,Bracher, A.,Hausch, F.
Rational Design and Asymmetric Synthesis of Potent and Neurotrophic Ligands for FK506-Binding Proteins (FKBPs).
Angew.Chem.Int.Ed.Engl., 54:345-348, 2015

PubMed Abstract: To create highly efficient inhibitors for FK506-binding proteins, a new asymmetric synthesis for pro-(S)-C(5) -branched [4.3.1] aza-amide bicycles was developed. The key step of the synthesis is an HF-driven N-acyliminium cyclization. Functionalization of the C(5)  moiety resulted in novel protein contacts with the psychiatric risk factor FKBP51, which led to a more than 280-fold enhancement in affinity. The most potent ligands facilitated the differentiation of N2a neuroblastoma cells with low nanomolar potency.

PubMed: 25412894
DOI: 10.1002/anie.201408776

実験手法

X-RAY DIFFRACTION (1.5 Å)