|3o5l, resolution 1.30Å ()|
|Gene:||AIG6, FKBP5, FKBP51 (Homo sapiens)|
|Related:||3o5d, 3o5e, 3o5f, 3o5g, 3o5i, 3o5j, 3o5k, 3o5m, 3o5o, 3o5p, 3o5q, 3o5r, 1kt0|
Fk1 domain mutant A19T 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.
Structural characterization of the PPIase domain of FKBP51, a cochaperone of human Hsp90., Bracher A, Kozany C, Thost AK, Hausch F, Acta Crystallogr D Biol Crystallogr. 2011 Jun;67(Pt 6):549-59. Epub 2011 May 17. PMID:21636895
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.