8R5K
The Fk1 domain of FKBP51 in complex with Antascomicine B
Summary for 8R5K
| Entry DOI | 10.2210/pdb8r5k/pdb |
| Descriptor | Peptidyl-prolyl cis-trans isomerase FKBP5, Antascomicine B (3 entities in total) |
| Functional Keywords | isomerase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14701.93 |
| Authors | |
| Primary citation | Schafer, S.C.,Voll, A.M.,Bracher, A.,Ley, S.V.,Hausch, F. Antascomicin B stabilizes FKBP51-Akt1 complexes as a molecular glue. Bioorg.Med.Chem.Lett., 104:129728-129728, 2024 Cited by PubMed Abstract: Antascomicin B is a natural product that similarly to the macrolides FK506 and Rapamycin binds to the FK506-binding protein 12 (FKBP12). FK506 and Rapamycin act as molecular glues by inducing ternary complexes between FKBPs and additional target proteins. Whether Antascomicin B can induce ternary complexes is unknown. Here we show that Antascomicin B binds tightly to larger human FKBP homologs. The cocrystal structure of FKBP51 in complex with Antascomicin B revealed that large parts of Antascomicin B are solvent-exposed and available to engage additional proteins. Cellular studies demonstrated that Antascomicin B enhances the interaction between human FKBP51 and human Akt. Our studies show that molecules with molecular glue-like properties are more prominent in nature than previously thought. We predict the existence of additional 'orphan' molecular glues that evolved to induce ternary protein complexes but where the relevant ternary complex partners are unknown. PubMed: 38582133DOI: 10.1016/j.bmcl.2024.129728 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.89 Å) |
Structure validation
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