FKBP12: Proteins and Enzymes

FK506 binding protein, also called FKBP12 and FKBP1A, was originally characterized as a peptidyl-prolyl isomerase that catalyzes the transition between cis- and trans-proline residues critical for proper folding of proteins. The macrolide immunosuppressants FK506 (Tacrolimus) and rapamycin bind to FKBP12 with high affinity, while the structurally related-compound cyclosporine binds with a much lower affinity. The binding of these drugs causes FKBP12 to become a potent inhibitor of calcineurin phosphatase activity and TOR kinase activity. Knockout mice lacking FKBP12 are morphologically normal, but develop cardiomyopathies that may be related to dysregulation of ryanodyne receptors.