3O5G: Fk1 Domain Of Fkbp51, Crystal Form I

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.
PDB ID: 3O5GDownload
MMDB ID: 90958
PDB Deposition Date: 2010/7/28
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 3O5G: monomeric; determined by author and by software (PISA)
Molecular Components in 3O5G
Label Count Molecule
Protein (1 molecule)
Peptidyl-prolyl Cis-trans Isomerase Fkbp5(Gene symbol: FKBP5)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB