3O5I

Fk1 domain of FKBP51, crystal form II

Summary for 3O5I

• Entry DOI: 10.2210/pdb3o5i/pdb
• Related: 1KT0 3O5D 3O5E 3O5F 3O5G 3O5J 3O5K 3O5L 3O5M 3O5O 3O5P 3O5Q 3O5R
• Descriptor: Peptidyl-prolyl cis-trans isomerase FKBP5, GLYCEROL, ACETATE ION, ... (4 entities in total)
• Functional Keywords: fk-506 binding domain, hsp90 cochaperone, immunophiline, peptidyl-prolyl isomerase, isomerase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q13451
• Total number of polymer chains: 2
• Total formula weight: 28143.24

Authors

Bracher, A.,Kozany, C.,Thost, A.-K.,Hausch, F. (deposition date: 2010-07-28, release date: 2011-06-01, Last modification date: 2023-09-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)