4DRQ

Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52: Complex of FKBP51 with 2-(3-((R)-1-((S)-1-(3,5-dichlorophenylsulfonyl)piperidine-2-carbonyloxy)-3-(3,4-dimethoxy -phenyl)propyl)phenoxy)acetic acid

4DRQ の概要

• エントリーDOI: 10.2210/pdb4drq/pdb
• 関連するPDBエントリー: 4DRK 4DRM 4DRN 4DRo 4DRp
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP5, {3-[(1S)-1-[({(2S)-1-[(3,5-dichlorophenyl)sulfonyl]piperidin-2-yl}carbonyl)oxy]-3-(3,4-dimethoxyphenyl)propyl]phenoxy}acetic acid (3 entities in total)
• 機能のキーワード: fk-506 binding domain, hsp90 cochaperone, immunophilin, peptidyl-prolyl isomerase, 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: 14692.64

構造登録者

Gopalakrishnan, R.,Kozany, C.,Wang, Y.,Hoogeland, B.,Bracher, A.,Hausch, F.,Schneider, S. (登録日: 2012-02-17, 公開日: 2012-04-18, 最終更新日: 2023-09-13)

主引用文献

Gopalakrishnan, R.,Kozany, C.,Wang, Y.,Schneider, S.,Hoogeland, B.,Bracher, A.,Hausch, F.
Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52.
J.Med.Chem., 55:4123-4131, 2012

PubMed Abstract: FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products, which tightly bind to most FKBP family members, including FKBP51 and FKBP52. A bioisosteric replacement of the α-ketoamide moiety of rapamycin and FK506 with a sulfonamide was envisaged with the retention of the conserved hydrogen bonds. A focused solid support-based synthesis protocol was developed, which led to ligands with submicromolar affinity for FKBP51 and FKBP52. The molecular binding mode for one sulfonamide analogue was confirmed by X-ray crystallography.

PubMed: 22455398
DOI: 10.1021/jm201747c

実験手法

X-RAY DIFFRACTION (1 Å)