Xu R X, Nettesheim D, Olejniczak E T, Meadows R, Gemmecker G, Fesik S W
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Biopolymers. 1993 Apr;33(4):535-50. doi: 10.1002/bip.360330404.
The 1H, 13C, and 15N resonances of FKBP when bound to the immunosuppressant, ascomycin, were assigned using a computer-aided analysis of heteronuclear double and triple resonance three-dimensional nmr spectra of [U-15N]FKBP/ascomycin and [U-15N,13C]FKBP/ascomycin. In addition, from a preliminary analysis of two heteronuclear four-dimensional data sets, 3JHN,H alpha coupling constants, amide exchange data, and the differences between the C alpha and C beta chemical shifts of FKBP to random coil values, the secondary structure of FKBP when bound to ascomycin was determined. The secondary structure of FKBP when bound to ascomycin in solution closely resembled the x-ray structure of the FKBP/FK506 complex but differed in some aspects from the structure of uncomplexed FKBP in solution.
当FKBP与免疫抑制剂子囊霉素结合时，通过对[U-15N]FKBP/子囊霉素和[U-15N,13C]FKBP/子囊霉素的异核双共振和三共振三维核磁共振谱进行计算机辅助分析，确定了FKBP的1H、13C和15N共振峰。此外，通过对两个异核四维数据集的初步分析、3JHN,Hα耦合常数、酰胺交换数据以及FKBP的Cα和Cβ化学位移与无规卷曲值之间的差异，确定了FKBP与子囊霉素结合时的二级结构。溶液中FKBP与子囊霉素结合时的二级结构与FKBP/FK506复合物的X射线结构非常相似，但在某些方面与溶液中未复合的FKBP结构不同。
