3O5L

Fk1 domain mutant A19T of FKBP51, crystal form I

3O5L の概要

• エントリーDOI: 10.2210/pdb3o5l/pdb
• 関連するPDBエントリー: 1KT0 3O5D 3O5E 3O5F 3O5G 3O5I 3O5J 3O5K 3O5M 3O5O 3O5P 3O5Q 3O5R
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP5, PENTAETHYLENE GLYCOL (3 entities in total)
• 機能のキーワード: fk-506 binding domain, hsp90 cochaperone, immunophiline, 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: 14264.35

構造登録者

Bracher, A.,Kozany, C.,Thost, A.-K.,Hausch, F. (登録日: 2010-07-28, 公開日: 2011-06-01, 最終更新日: 2023-09-06)

主引用文献

Bracher, A.,Kozany, C.,Thost, A.K.,Hausch, F.
Structural characterization of the PPIase domain of FKBP51, a cochaperone of human Hsp90.
Acta Crystallogr.,Sect.D, 67:549-559, 2011

PubMed Abstract: Steroid hormone receptors are key components of mammalian stress and sex hormone systems. Many of them rely on the Hsp90 chaperone system for full function and are further fine-tuned by Hsp90-associated peptidyl-prolyl isomerases such as FK506-binding proteins 51 and 52. FK506-binding protein 51 (FKBP51) has been shown to reduce glucocorticoid receptor signalling and has been genetically associated with human stress resilience and with numerous psychiatric disorders. The peptidyl-prolyl isomerase domain of FKBP51 contains a high-affinity binding site for the natural products FK506 and rapamycin and has further been shown to convey most of the inhibitory activity on the glucocorticoid receptor. FKBP51 has therefore become a prime new target for the treatment of stress-related affective disorders that could be amenable to structure-based drug design. Here, a series of high-resolution structures of the peptidyl-prolyl isomerase domain of FKBP51 as well as a cocrystal structure with the prototypic ligand FK506 are described. These structures provide a detailed picture of the drug-binding domain of FKBP51 and the molecular binding mode of its ligand as a starting point for the rational design of improved inhibitors.

PubMed: 21636895
DOI: 10.1107/S0907444911013862

実験手法

X-RAY DIFFRACTION (1.3 Å)