title: Effect of selected phytotoxins from Guanomyces polythrix on the calmodulin-dependent activity of the enzymes cAMP phosphodiesterase and NAD-kinase.
abstract: The effect of a series of phytotoxins isolated from the fungus Guanomyces polytrix on calmodulin (CaM)-dependent nicotinamide adenine dinucleotide kinase (NADK) and CaM-dependent cyclic nucleotide phosphodiesterase (PDE) activities was investigated. The results indicated that (2S,3S)-5-hydroxy-6,8-dimethoxy-2,3-dimethyl-4H-2,3-dihydronaphtho[2,3-b]-pyran-4-one, (2S,3S)-5-hydroxy-6,8,10-trimethoxy-2,3-dimethyl-4H-2,3-dihydro-naphtho[2,3-b]-pyran-4-one, (2S,3R)-5-hydroxy-6,8-dimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one, (2S,3R)-5-hydroxy-6,8,10-trime-thoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one, 5-hydro-xy-6,8-dimethoxy-2,3-dimethyl-4H-naphtho[2,3-b]-pyran-4-one, rubrofusarin B, and ergosta-4,6,8(14),22-tetraen-3-one inhibited the activation of both target enzymes in the presence of CaM. On the other hand, (2S)-5-hydroxy-6,8-dimethoxy-2-methyl-4H-2,3-dihydronaphtho[2,3-b]-pyran-4-one and (2S)-5-hydroxy-6,8,10-trimethoxy-2-methyl-4H-2,3-dihydronaphtho-[2,3-b]-pyran-4-one inhibited the activation of PDE and the basal activity of NADK. Thus, these phytotoxins are CaM inhibitors and may exert their phytotoxic action by inhibiting the CaM-dependent process, although they could also interfere with other cellular metabolic phenomena. This is the first report of the use of the NADK assay to detect or quantify CaM inhibitors, and it could be a valuable tool for studying those CaM isoforms regulating NADK.
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico. rachel@servidor.unam.mx
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
authors.forename: Alicia
authors.initials: A
authors.lastname: Gamboa
authors.forename: Martha
authors.initials: M
authors.lastname: Macias
authors.forename: Sandra
authors.initials: S
authors.lastname: Santillán
authors.forename: Miguel
authors.initials: M
authors.lastname: Ulloa
authors.forename: María del Carmén
authors.initials: Mdel C
authors.lastname: González
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002147:Calmodulin / Q000494:pharmacology*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006540:Herbicides / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010944:Plants / Q000187:drug effects* / Q000201:enzymology; D020037:Sordariales / Q000737:chemistry*
chemical_list: D002147:Calmodulin; D004791:Enzyme Inhibitors; D006540:Herbicides; D017853:Phosphotransferases (Alcohol Group Acceptor); C021844:NAD kinase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1