Abstract
Nitric oxide (NO) is a pluripotent regulatory molecule showing, among others, an antiparasitic activity. Moreover, NO inhibits cysteine proteinase action by nitrosylating the Cys catalytic residue. In the present study, the inhibitory effect of the substrate N-α-benzyloxycarbonyl-L-phenylalanyl-L-arginine-(7-amino-4-methylcoumarin) and of NO on the catalytic activity of cruzipain, the major papain-like cysteine proteinase from Trypanosoma cruzi (the hemoflagellate protozoan parasite which causes the American trypanosomiasis), is reported. In particular, NO-donors S-nitroso-glutathione (GSNO), (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3), 3-morpholinosydnonimine (SIN-1), S-nitroso-acetyl-penicillamine (SNAP), and sodium nitroprusside (SNP) dose-dependently inhibited cruzipain, this effect being likely attributable to the S-nitrosylation of the Cys25 catalytic residue. These results were analyzed in parallel with those concerning the inhibitory effect of the substrate and of NO on the catalytic activity of falcipain, the cruzipain-homologous cysteine proteinase from Plasmodium falciparum. The modulation of the cruzipain and falcipain activity by NO may be relevant in developing new strategies against T. cruzi and P. falciparum in human host. As a whole, the NO-mediated S-nitrosylation of pathogenic viral, bacterial, fungal, and parasitic cysteine proteinases may represent a general mechanism of antimicrobial and antiparasitic host defences. (C) 2000 Academic Press.
| Original language | English |
|---|---|
| Pages (from-to) | 437-441 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 270 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 13 2000 |
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Keywords
- Cruzipain
- Enzyme inhibition
- Falcipain
- NO-donor
- Papain-like cysteine proteinase
- Plasmodium falciparum
- Substrate
- Trypanosoma cruzi
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Nitric oxide inhibits cruzipain, the major papain-like cysteine proteinase from Trypanosoma cruzi. / Venturini, Giorgio; Salvati, Luca; Muolo, Massimo; Colasanti, Marco; Gradoni, Luigi; Ascenzi, Paolo.
In: Biochemical and Biophysical Research Communications, Vol. 270, No. 2, 13.04.2000, p. 437-441.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Nitric oxide inhibits cruzipain, the major papain-like cysteine proteinase from Trypanosoma cruzi
AU - Venturini, Giorgio
AU - Salvati, Luca
AU - Muolo, Massimo
AU - Colasanti, Marco
AU - Gradoni, Luigi
AU - Ascenzi, Paolo
PY - 2000/4/13
Y1 - 2000/4/13
N2 - Nitric oxide (NO) is a pluripotent regulatory molecule showing, among others, an antiparasitic activity. Moreover, NO inhibits cysteine proteinase action by nitrosylating the Cys catalytic residue. In the present study, the inhibitory effect of the substrate N-α-benzyloxycarbonyl-L-phenylalanyl-L-arginine-(7-amino-4-methylcoumarin) and of NO on the catalytic activity of cruzipain, the major papain-like cysteine proteinase from Trypanosoma cruzi (the hemoflagellate protozoan parasite which causes the American trypanosomiasis), is reported. In particular, NO-donors S-nitroso-glutathione (GSNO), (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3), 3-morpholinosydnonimine (SIN-1), S-nitroso-acetyl-penicillamine (SNAP), and sodium nitroprusside (SNP) dose-dependently inhibited cruzipain, this effect being likely attributable to the S-nitrosylation of the Cys25 catalytic residue. These results were analyzed in parallel with those concerning the inhibitory effect of the substrate and of NO on the catalytic activity of falcipain, the cruzipain-homologous cysteine proteinase from Plasmodium falciparum. The modulation of the cruzipain and falcipain activity by NO may be relevant in developing new strategies against T. cruzi and P. falciparum in human host. As a whole, the NO-mediated S-nitrosylation of pathogenic viral, bacterial, fungal, and parasitic cysteine proteinases may represent a general mechanism of antimicrobial and antiparasitic host defences. (C) 2000 Academic Press.
AB - Nitric oxide (NO) is a pluripotent regulatory molecule showing, among others, an antiparasitic activity. Moreover, NO inhibits cysteine proteinase action by nitrosylating the Cys catalytic residue. In the present study, the inhibitory effect of the substrate N-α-benzyloxycarbonyl-L-phenylalanyl-L-arginine-(7-amino-4-methylcoumarin) and of NO on the catalytic activity of cruzipain, the major papain-like cysteine proteinase from Trypanosoma cruzi (the hemoflagellate protozoan parasite which causes the American trypanosomiasis), is reported. In particular, NO-donors S-nitroso-glutathione (GSNO), (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3), 3-morpholinosydnonimine (SIN-1), S-nitroso-acetyl-penicillamine (SNAP), and sodium nitroprusside (SNP) dose-dependently inhibited cruzipain, this effect being likely attributable to the S-nitrosylation of the Cys25 catalytic residue. These results were analyzed in parallel with those concerning the inhibitory effect of the substrate and of NO on the catalytic activity of falcipain, the cruzipain-homologous cysteine proteinase from Plasmodium falciparum. The modulation of the cruzipain and falcipain activity by NO may be relevant in developing new strategies against T. cruzi and P. falciparum in human host. As a whole, the NO-mediated S-nitrosylation of pathogenic viral, bacterial, fungal, and parasitic cysteine proteinases may represent a general mechanism of antimicrobial and antiparasitic host defences. (C) 2000 Academic Press.
KW - Cruzipain
KW - Enzyme inhibition
KW - Falcipain
KW - NO-donor
KW - Papain-like cysteine proteinase
KW - Plasmodium falciparum
KW - Substrate
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=0034643269&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034643269&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2000.2447
DO - 10.1006/bbrc.2000.2447
M3 - Article
C2 - 10753643
AN - SCOPUS:0034643269
VL - 270
SP - 437
EP - 441
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -