3FAP

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

3FAP の概要

• エントリーDOI: 10.2210/pdb3fap/pdb
• 関連するPDBエントリー: 2FAP 4FAP
• 分子名称: FK506-BINDING PROTEIN, FKBP12-RAPAMYCIN ASSOCIATED PROTEIN, C15-(R)-METHYLTHIENYL RAPAMYCIN, ... (4 entities in total)
• 機能のキーワード: fkbp12, frap, rapamycin, complex, gene therapy, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P62942; Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P42345
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24148.74

構造登録者

Liang, J.,Clardy, J. (登録日: 1999-05-06, 公開日: 2000-09-13, 最終更新日: 2023-09-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)