9EY3
The FK1 domain of FKBP51 in complex with (3S,11S,11aS)-12-((3,5-dichlorophenyl)sulfonyl)-5-oxo-11-vinyldecahydro-1H-6,10-epiminopyrrolo[1,2-a]azonine-3-carboxylic acid
This is a non-PDB format compatible entry.
Summary for 9EY3
| Entry DOI | 10.2210/pdb9ey3/pdb |
| Descriptor | Peptidyl-prolyl cis-trans isomerase FKBP5, (1~{S},4~{S},7~{S},8~{S},9~{R})-13-[3,5-bis(chloranyl)phenyl]sulfonyl-8-ethenyl-2-oxidanylidene-3,13-diazatricyclo[7.3.1.0^{3,7}]tridecane-4-carboxylic acid (3 entities in total) |
| Functional Keywords | fkbp51, inhibitor, complex, isomerase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14477.40 |
| Authors | Meyners, C.,Krajczy, P.,Hausch, F. (deposition date: 2024-04-09, release date: 2024-06-12, Last modification date: 2024-08-28) |
| Primary citation | Krajczy, P.,Meyners, C.,Repity, M.L.,Hausch, F. Structure-Based Design of Ultrapotent Tricyclic Ligands for FK506-Binding Proteins. Chemistry, 30:e202401405-e202401405, 2024 Cited by PubMed Abstract: Access to small, rigid, and sp-rich molecules is a major limitation in the drug discovery for challenging protein targets. FK506-binding proteins hold high potential as drug targets or enablers of molecular glues but are fastidious in the chemotypes accepted as ligands. We here report an enantioselective synthesis of a highly rigidified pipecolate-mimicking tricyclic scaffold that precisely positions functional groups for interacting with FKBPs. This was enabled by a 14-step gram-scale synthesis featuring anodic oxidation, stereospecific vinylation, and N-acyl iminium cyclization. Structure-based optimization resulted in the discovery of FKBP inhibitors with picomolar biochemical and subnanomolar cellular activity that represent the most potent FKBP ligands known to date. PubMed: 38837733DOI: 10.1002/chem.202401405 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.16 Å) |
Structure validation
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