X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex

@article{Griffith1995XraySO,
  title={X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex},
  author={James P. Griffith and Joseph L. Kim and Eunice EunKyeong Kim and Michael D. Sintchak and John A. Thomson and Matthew J. Fitzgibbon and Mark A. Fleming and Paul R. Caron and Kathy Hsiao and Manuel A. Navia},
  journal={Cell},
  year={1995},
  volume={82},
  pages={507-522}
}
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The structure of the human FK506 binding protein (FKBP), complexed with the immunosuppressant FK506, has been determined to 1.7 angstroms resolution by x-ray crystallography. The conformation of the…
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
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It is suggested that immunosuppressive ligands express their differential effects in part by modulating the conformation of FKBP12, in agreement with mutagenesis experiments on the protein, and not simply through differences in the ligand structures themselves.
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High resolution structures for the complexes formed by the immunosuppressive agents FK506 and rapamycin with the human immunophilin FKBP-12 have been determined by X-ray diffraction and suggest ways in which this catalytic activity could operate.
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The results show that calcineurin is a target of drug-immunophilin complexes in vivo and establish a physiological role for calcium-dependent serine/threonine phosphatase in T-cell activation.
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It is reported here that overexpression of calcineurin in Jurkat cells renders them more resistant to the effects of CsA and FK506 and augments both NFAT- and NFIL2A-dependent transcription.
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