8R5K

The Fk1 domain of FKBP51 in complex with Antascomicine B

8R5K の概要

• エントリーDOI: 10.2210/pdb8r5k/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP5, Antascomicine B (3 entities in total)
• 機能のキーワード: isomerase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14701.93

構造登録者

Voll, M.A.,Bracher, A.,Hausch, F. (登録日: 2023-11-16, 公開日: 2024-05-08)

主引用文献

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

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: 38582133
DOI: 10.1016/j.bmcl.2024.129728

実験手法

X-RAY DIFFRACTION (0.89 Å)