3O5P: Fk1 Domain Mutant A19t Of Fkbp51, Crystal Form Iv

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: 3O5PDownload
MMDB ID: 90965
PDB Deposition Date: 2010/7/28
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 1  Å
Source Organism:
Similar Structures:
Biological Unit for 3O5P: monomeric; determined by author and by software (PISA)
Molecular Components in 3O5P
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