mTOR domain structure, complexes and downstream signaling. mTOR is a 289-kDa serine/threonine protein kinase, containing multiple domains which include the FAT domain, the FKBP12-rapamycin binding domain (FRB), the kinase domain, the FATC domain and at least 20 HEAT repeats, which provide ...
We previously advanced an inducible dimerization system into an inducible oligomerization system by developing a bivalent fusion protein, FRB–FKBP, which forms large oligomers upon rapamycin addition and can be used to manipulate cells. However, the oligomeric structure of FRB–FKBP remains unclear. ...
The structure of the FKBP12–rapamycin–FRB ternary complex has now been refined at 2.2 Å resolution. The cell-cycle arrest agent rapamycin binds FK506-binding protein (FKBP12) and the FKBP12–rapamycin binding (FRB) domain of FKBP12–rapamycin associated protein (FRAP) simultaneously, and...
crystal structure (Protein Data Bank (PDB) ID:4LAV) (ref.46) and adopting different interfaces with GR (Supplementary Movies3and4). In the consensus 3D refinement map, the proline-rich loop adopts a position similar to the crystal structure, and FKBP52A116,S118,P119interact with GRHelix5...
research papers Re 庐 ned structure of the FKBP12 卤 rapamycin 卤 FRB 脢 resolution ternary complex at 2 . 2 A research papersLiang, JunChoi, JungwonClardy, Jon
We also successfully demonstrated the visualization of the rapamycin-mediated complexation of the OG-FKBP12 and FRB inside of living cells by the combined use with fluorescent protein-tag technology and Frster resonance energy-transfer imaging. 展开 ...
FKBP51 has been seen in a complex with FRB domain of human mTOR and in our native structure we noticed that the Arg73 is not in the same position as in the FKBP51-FRB complex (PDB ID:4DRI)36. This particular arginine is missing in the previously reported structure of FKBP51 and the...
(1996) Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science 273, 239 -242Choi, J., Chen, J., Schreiber, S.L., Clardy, J., 1996. Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science 273, ...
ligand with docking score values of 33.4 (3CQU-3D structure of AKT1)] and 27.3 (2FAP-3D structure of FRB domain of mTOR) respectively as compared to that of standard drug Everolimus with 24.4 (3CQU-3D structure of AKT1) and 20.1 (2FAP-3D structure of FRB domain of mTOR) respectively....
The crystal structure of the ternary complex revealed that the hit targeted a similar surface on the FRB domain compared to natural product rapamycin but with a radically different interaction pattern. Structure-guided optimization improved potency 500-fold, and led to compounds which initiate FKBP12-...