title: PDE7A1 hydrolyzes cCMP.
abstract: 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 KM value of 135 ± 19 μM. The Vmax for cCMP hydrolysis reached 745 ± 27 nmol/(minmg), 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.
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Monzel
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; Core Facility Mass Spectrometry and Metabolomics, Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bähre
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
authors.affiliation: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Erich H
authors.initials: EH
authors.lastname: Schneider
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000737:chemistry; D003563:Cyclic CMP / Q000737:chemistry*; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009574:Nitro Compounds / Q000737:chemistry; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry; D015290:Second Messenger Systems; D061987:Sf9 Cells; D018411:Spodoptera; D013379:Substrate Specificity; D013449:Sulfonamides / Q000737:chemistry
chemical_list: C497936:3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene; D009574:Nitro Compounds; D010726:Phosphodiesterase Inhibitors; D013449:Sulfonamides; D003563:Cyclic CMP; D000242:Cyclic AMP; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517458:PDE7A protein, human
keywords: Cyclic CMP; Cyclic nucleotides; Enzyme kinetics; HPLC–MS; Phosphodiesterase; Second messenger