Structural highlights
4drq is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Related: | 4drk, 4drm, 4drn, 4dro, 4drp |
| Gene: | AIG6, FKBP5, FKBP51 (HUMAN) |
| Activity: | Peptidylprolyl isomerase, with EC number 5.2.1.8 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[FKBP5_HUMAN] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.
Publication Abstract from PubMed
FK506-binding proteins (FKBP) 51 and 52 are co-chaperones that modulate the signal transduction of steroid hormone receptors. Single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products, which tightly bind to all these proteins. A bio-isosteric replacement of the alpha-ketoamide moiety of rapamycin and FK506 with a sulfonamide was envisaged with the retention of the conserved hydrogen bonds. A focused solid support-based synthesis protocol was developed, which led to ligands with submicromolar affinity for FKBP51 and FKBP52. The molecular binding mode for one sulfonamide analog was confirmed by X-ray crystallography.
Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52.,Gopalakrishnan R, Kozany C, Wang Y, Schneider S, Hoogeland B, Bracher A, Hausch F J Med Chem. 2012 Mar 29. PMID:22455398[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gopalakrishnan R, Kozany C, Wang Y, Schneider S, Hoogeland B, Bracher A, Hausch F. Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52. J Med Chem. 2012 Mar 29. PMID:22455398 doi:10.1021/jm201747c
