5DIT

The Fk1 domain of FKBP51 in complex with the new synthetic ligand (1R)-3-(3,4-dimethoxyphenyl)-1-f3-[2-(morpholin-4-yl)ethoxy]phenylgpropyl(2S)-1-[(2S,3R)-2-cyclohexyl-3-hydroxybutanoyl]piperidine-2-carboxylate

5DIT の概要

• エントリーDOI: 10.2210/pdb5dit/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP5, (1R)-3-(3,4-dimethoxyphenyl)-1-{3-[2-(morpholin-4-yl)ethoxy]phenyl}propyl (2S)-1-[(2S,3R)-2-cyclohexyl-3-hydroxybutanoyl]piperidine-2-carboxylate (3 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: 1
• 化学式量合計: 14706.95

構造登録者

Feng, X.,Sippel, C.,Bracher, A.,Hausch, F. (登録日: 2015-09-01, 公開日: 2015-10-14, 最終更新日: 2024-05-08)

主引用文献

Feng, X.,Sippel, C.,Bracher, A.,Hausch, F.
Structure-Affinity Relationship Analysis of Selective FKBP51 Ligands.
J.Med.Chem., 58:7796-7806, 2015

PubMed Abstract: The FK506-binding protein 51 (FKBP51) is a promising drug target for the treatment of stress-related psychiatric or metabolic disorders. Just recently, the first selective ligands for FKBP51 were reported based on an induced fit mechanism, but they are too large for a further drug development process. We therefore designed and synthesized a novel series of selective ligands to explore the requirements necessary for binding to the induced-fit conformation. All ligands of this series show no binding toward the structurally very similar antitarget FKBP52. With the cocrystal structure of the best ligand in this novel series we confirmed the induced fit mechanism. Furthermore, the structure-affinity relationship provides information about beneficial structural features, which is valuable for the development of improved FKBP51-directed drugs.

PubMed: 26419422
DOI: 10.1021/acs.jmedchem.5b00785

実験手法

X-RAY DIFFRACTION (2.25 Å)