1NSG: THE STRUCTURE OF THE IMMUNOPHILIN-IMMUNOSUPPRESSANT FKBP12-RAPAMYCIN COMPLEX INTERACTING WITH HUMAN FRAP

Citation:
Abstract
The structure of the FKBP12-rapamycin-FRB ternary complex has now been refined at 2.2 A 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 the inhibition of FRAP is responsible for rapamycin's biological activity. The conformation of rapamycin in the ternary complex is very similar to that observed in the FKBP12-rapamycin binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9 degrees ) rotation repositions the FRB-binding face of rapamycin in the ternary complex. There are extensive rapamycin-protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, these interactions mainly involving residues in the 40s and 80s loops of FKBP12 and alpha1 and alpha4 of FRB. The high-resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.
PDB ID: 1NSGDownload
MMDB ID: 7282
PDB Deposition Date: 1997/7/1
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 1NSG: dimeric; determined by author
Molecular Components in 1NSG
Label Count Molecule
Proteins (2 molecules)
1
Fk506-binding Protein(Gene symbol: FKBP1A)
Molecule annotation
1
Fkbp-rapamycin Associated Protein (Frap)(Gene symbol: MTOR)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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