The N-terminal domain influences the structure and property of protein phosphatase 1.

The protein phosphatase 1 has conserved cores in PPP gene family flanked by non-conserved N-terminal domains. PP1 with residues 1-8 deleted or substituted by residues 1-42 of calcineurin catalytic subunit were designated PP1-(9-330) and CNA(1-42)-PP1(9-330), respectively. When compared with PP1, PP1-(9-330) had higher and CNA(1-42)-PP1(9-330) had lower activity with three kinds of substrates; PP1-(9-330) has higher and CNA(1-42)-PP1(9-330) has lower sensitivity to okadaic acid.

The nonconserved N-terminus of protein phosphatase 2B confers its properties to protein phosphatase 1.

The protein phosphatase 1 catalytic subunit (PP1c) and the protein phosphatase 2B (PP2B or calcineurin) catalytic subunit (CNA) contain nonconserved N-terminal regions followed by conserved phosphatase cores. To examine the role of the N-termini of these two phosphatases, we substituted the residues 1-8 of PP1c with residues 1-42 of CNA, which is designated CNA(1-42)-PP1(9-330). The activities of CNA(1-42)-PP1(9-330) were similar to those of PP2B and different from those of PP1.

The beta12-beta13 loop is a key regulatory element for the activity and properties of the catalytic domain of protein phosphatase 1 and 2B.

The molecular architectures of the catalytic core of protein phosphatase 1 (PP1) and protein phosphatase 2B (PP2B) are similar, and both contain a beta12-beta13 loop that consists of non-conserved residues. A truncation mutant containing the PP2B catalytic domain has previously been constructed in our laboratory, and designated CNAa. In this study, the PP1 catalytic subunit (PP1c) and CNAa, as well as mutants with the corresponding loops exchanged, were investigated using multiple substrates.