Structural studies on FK-506, cyclosporin A and their immunophilin complexes

Summary

The immunosuppressants FK-506 and cyclosporin A (CsA), along with their macromolecular receptors FKBP12 and cyclophilin A (CyPA), have become important targets for structure-based drug design. In the last few years X-ray diffraction and NMR spectroscopy have combined to provide high-resolution structures of FK-506, CyA, FKBP12, CyPA, FKBP12-FK-506, CyPA-CyA, and other complexes. This review summarizes these structural studies and some of their implications. Because the immunosuppressant-immunophilin complex forms a composite binding surface that interacts with yet another protein, structure-based drug design in this area is unusually challenging.

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Clardy, J. Structural studies on FK-506, cyclosporin A and their immunophilin complexes. Perspectives in Drug Discovery and Design 2, 127–144 (1994). https://doi.org/10.1007/BF02171740

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Key words

  • Immunophilin
  • FK-506 binding protein
  • FKBP
  • Cyclophilin
  • X-ray structure
  • Active site-ligand interactions
  • Calcineurin