title: Nitric oxide inhibits falcipain, the Plasmodium falciparum trophozoite cysteine protease.
abstract: Nitric oxide (NO) is a pluripotent regulatory molecule possessing, among others, an antiparasitic activity. In the present study, the inhibitory effect of NO on the catalytic activity of falcipain, the papain-like cysteine protease involved in Plasmodium falciparum trophozoite hemoglobin degradation, is reported. In particular, NO donors S-nitrosoglutathione (GSNO), (+/-)-(E)-p6ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenami  de (NOR-3), 3-morpholinosydnonimine (SIN-1), and sodium nitroprusside (SNP) inhibit dose-dependently the falcipain activity present in the P. falciparum trophozoite extract, this effect likely attributable to S-nitrosylation of the Cys25 catalytic residue. The results represent a new insight into the modulation mechanism of falcipain activity, thereby being relevant in developing new strategies for inhibition of the P. falciparum life cycle.
authors.affiliation: Dipartimento di Biologia, Università di Roma "Tre,", Viale Guglielmo Marconi 446, Rome, I-00146, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Venturini
authors.forename: M
authors.initials: M
authors.lastname: Colasanti
authors.forename: L
authors.initials: L
authors.lastname: Salvati
authors.forename: L
authors.initials: L
authors.lastname: Gradoni
authors.forename: P
authors.initials: P
authors.lastname: Ascenzi
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000201:enzymology*; D026422:S-Nitrosoglutathione
chemical_list: D015853:Cysteine Proteinase Inhibitors; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D009603:Nitroso Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C002385:linsidomine; C061872:FK 409; D008981:Molsidomine; D003546:Cysteine Endopeptidases; C099607:falcipain; D005978:Glutathione; D004229:Dithiothreitol