PDE7A1 hydrolyzes cCMP

The degradation and biological role of the cyclic pyrimidine nucleotide cCMP is largely elusive. We investigated nucleoside 3',5'-cyclic monophosphate (cNMP) specificity of six different recombinant phosphodiesterases (PDEs) by using a highly-sensitive HPLC-MS/MS detection method. PDE7A1 was the only enzyme that hydrolyzed significant amounts of cCMP. Enzyme kinetic studies using purified GST-tagged truncated PDE7A1 revealed a cCMP K-M value of 135 +/- 19 mu M. The V-max for cCMP hydrolysis reached 745 +/- 27 nmol/(min mg), which is about 6-fold higher than the corresponding velocity for adenosine 3',5'-cyclic monophosphate (cAMP) degradation. In summary, PDE7A is a high-speed and low-affinity PDE for cCMP. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.