Nitric oxide inhibits falcipain, the Plasmodium falciparum trophozoite cysteine protease.
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.
Venturini
G
G
Dipartimento di Biologia, Università di Roma "Tre,", Viale Guglielmo Marconi 446, Rome, I-00146, Italy.
Colasanti
M
M
Salvati
L
L
Gradoni
L
L
Ascenzi
P
P
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
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