3FAP

ATOMIC STRUCTURES OF THE RAPAMYCIN ANALOGS IN COMPLEX WITH BOTH HUMAN FKBP12 AND FRB DOMAIN OF FRAP

Summary for 3FAP

• Entry DOI: 10.2210/pdb3fap/pdb
• Related: 2FAP 4FAP
• Descriptor: FK506-BINDING PROTEIN, FKBP12-RAPAMYCIN ASSOCIATED PROTEIN, C15-(R)-METHYLTHIENYL RAPAMYCIN, ... (4 entities in total)
• Functional Keywords: fkbp12, frap, rapamycin, complex, gene therapy, cell cycle
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P62942; Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P42345
• Total number of polymer chains: 2
• Total formula weight: 24148.74

Authors

Liang, J.,Clardy, J. (deposition date: 1999-05-06, release date: 2000-09-13, Last modification date: 2023-09-06)

Primary citation

Liang, J.,Choi, J.,Clardy, J.
Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.
Acta Crystallogr.,Sect.D, 55:736-744, 1999

PubMed 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.

PubMed: 10089303
DOI: 10.1107/S0907444998014747

Experimental method

X-RAY DIFFRACTION (1.85 Å)