4drp

Evaluation of Synthetic FK506 Analogs as Ligands for the FK506-Binding Proteins 51 and 52: Complex of FKBP51 with 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2S)-2-ethyl-1-hydroxy-cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid from cocrystallizationEvaluation of Synthetic FK506 Analogs as Ligands for the FK506-Binding Proteins 51 and 52: Complex of FKBP51 with 2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2S)-2-ethyl-1-hydroxy-cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid from cocrystallization

Structural highlights 4drp is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 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 The FK506-binding proteins (FKBP) 51 and 52 are cochaperones that modulate the signal transduction of steroid hormone receptors. Both proteins have been implicated in prostate cancer. Furthermore, 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 that bind to these proteins indiscriminately but with nanomolar affinity. We here report the cocrystal structure of FKBP51 with a simplified alpha-ketoamide analogue derived from FK506 and the first structure-activity relationship analysis for FKBP51 and FKBP52 based on this compound. In particular, the tert-pentyl group of this ligand was systematically replaced by a cyclohexyl ring system, which more closely resembles the pyranose ring in the high-affinity ligands rapamycin and FK506. The interaction with FKBPs was found to be surprisingly tolerant to the stereochemistry of the attached cyclohexyl substituents. The molecular basis for this tolerance was elucidated by X-ray cocrystallography. Evaluation of Synthetic FK506 Analogues as Ligands for the FK506-Binding Proteins 51 and 52.,Gopalakrishnan R, Kozany C, Gaali S, Kress C, Hoogeland B, Bracher A, Hausch F J Med Chem. 2012 May 10;55(9):4114-22. Epub 2012 Apr 19. PMID:22455444 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also FKBP 3D structures

spinqualitylabelsall models 4drp, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image