Nucleotidyl Cyclase Activity of Particulate Guanylyl Cyclase A: Comparison with Particulate Guanylyl Cyclases E and F, Soluble Guanylyl Cyclase and Bacterial Adenylyl Cyclases Cyaa and Edema Factor

摘要: Guanylyl cyclases (GCs) regulate many physiological processes by catalyzing the synthesis of second messenger cGMP. The GC family consists seven particulate GCs (pGCs) and a nitric oxide-activated soluble (sGC). Rat sGC α1β1 possesses much broader substrate specificity than previously assumed. Moreover, exotoxins CyaA from Bordetella pertussis edema factor (EF) Bacillus anthracis possess nucleotidyl cyclase (NC) activity. pGC-A is natriuretic peptide-activated homodimer with two catalytic sites that act cooperatively. Here, we studied NC activity rat in membranes stably transfected HEK293 cells using highly sensitive specific HPLC-MS/MS technique. GTP ITP were effective, ATP XTP only poor, substrates. In contrast to sGC, did not use CTP UTP as pGC-E pGC-F expressed bovine rod outer segment used substrate. intact cells, generated pGCs, EF showed very broad substrate-specificity. conclusion, NCs exhibit different substrate-specificities, arguing against substrate-leakiness enzymes pointing distinct functions cyclic purine pyrimidine nucleotides.