Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex

A study has been conducted to examine the crystal structures of human calcineurin, an important protein in T-cell activation, and the human binding protein complex, FKBP12-FK506, which inhibit calcineurin after association with cytoplasmic binding proteins. Electron microscopy showed that an autoinhibitory element binds calcineurin at the Zn/Fe-containing active site to induce nucleophilic attack on the substrate phosphate by a metal-activated water molecule. Since the auto-inhibitory element is displaced in the FK-506-calcineurin complex, the protein complex is forced to share a binding site with inhibitors of calcineurin.