Nitric oxide inhibits cruzipain, the major papain-like cysteine proteinase from Trypanosoma cruzi

Giorgio Venturini, Luca Salvati, Massimo Muolo, Marco Colasanti, Luigi Gradoni, Paolo Ascenzi

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)437-441
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume270
Issue number2
DOIs
Publication statusPublished - Apr 13 2000

Keywords

  • Cruzipain
  • Enzyme inhibition
  • Falcipain
  • NO-donor
  • Papain-like cysteine proteinase
  • Plasmodium falciparum
  • Substrate
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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