The regulatory domains of CNA have different effects on the inhibition of CN activity by FK506 and CsA.

Calcineurin (CN) is the common receptor for two immunophilin-immunosuppressant complexes, Cyp-CsA and FKBP-FK506. Calcineurin is composed of a catalytic subunit (CNA) and a regulatory subunit (CNB). CNA contains the catalytic domain and three regulatory domains: a CNB-binding domain (BBH, 350 - 370), a calmodulin- binding domain (CBD, 389 - 413), and an autoinhibitory domain (AID, 457 - 482). To investigate the effects of these three regulatory domains on the inhibition of CN by the two drugs we constructed three C-terminal deletion mutants: CNAabc (1 - 456), CNAab (1 - 388) and CNAa (1 - 347). Inhibition of CNA and its derivatives by the two drugs was examined and compared with inhibition by peptides (AID [457 - 482] and LCBD [389 - 456], CBD and the extension of the AID were included). Our results show that the BBH is critical for inhibition of CN by Cyp-CsA and FKBP-FK506. The LCBD has no effect and the AID reduces the inhibition of CN by two complexes. In addition, LCBD and AID as autoinhibitors may inhibit enzyme activity via different sites. IUBMB Life, 59: 388 - 393, 2007 [ABSTRACT FROM AUTHOR]