Nitric Oxide Inhibits Falcipain, the Plasmodium falciparum Trophozoite Cysteine Protease

Venturini, Giorgio; Colasanti, Marco; Salvati, Luca; Gradoni, Luigi; Ascenzi, Paolo

doi:10.1006/bbrc.1999.1922

Cited by 38 publications

(29 citation statements)

References 33 publications

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“…This species, which has been identified by spectroscopic and colorimetric quantitation techniques in a number of proteins, is reducible to the free thiol by DTT with the recovery of enzyme activity (42). This latter criterion has been used to postulate the presence of an S-nitrosothiol group in recent studies on the effects of NO donors on enzymes, sometimes in the absence of direct evidence (43)(44)(45). If NO donors used in the inactivation of cysteine-containing enzymes were compounds that release only nitric oxide as the inactivating reagent in the incubation (such as diazeniumdiolates, sodium nitroprusside, …”

Section: Resultsmentioning

confidence: 99%

Inhibition of Papain by S-Nitrosothiols

Xian

Chen

Liu

et al. 2000

Journal of Biological Chemistry

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S-Nitrosylation of protein thiols is one of the cellular regulatory mechanisms induced by NO. The cysteine protease papain has a critical thiol residue (Cys 25 ). It has been demonstrated that NO or NO donors such as sodium nitroprusside and N-nitrosoaniline derivatives can reversibly inhibit this enzyme by S-NO bond formation in its active site. In this study, a different regulated mechanism of inactivation was reported using S-nitrosothiols as the NO donor. Five S-nitroso compounds, Snitroso-N-acetyl-DL-penicillamine, S-nitrosoglutathione, S-nitrosocaptopril, glucose-S-nitroso-N-acetyl-DL-penicillamine-2, and the S-nitroso tripeptide acetyl-Phe-Gly-S-nitrosopenicillamine, exhibited different inhibitory activities toward the enzyme in a time-and concentrationdependent manner with second-order rate constants (k i / K I ) ranging from 8.9 to 17.2 M ؊1 s ؊1 . The inhibition of papain by S-nitrosothiol was rapidly reversed by dithiothreitol, but not by ascorbate, which could reverse the inhibition of papain by NOBF 4 . Incubation of the enzyme with a fluorescent S-nitroso probe (S-nitroso-5-dimethylaminonaphthalene-1-sulfonyl) resulted in the appearance of fluorescence of the protein, indicating the formation of a thiol adduct. Moreover, S-transnitrosylation in the incubation of S-nitroso inactivators with papain was excluded. These results suggest that inactivation of papain by S-nitrosothiols is due to a direct attack of the highly reactive thiolate (Cys 25 ) in the enzyme active site on the sulfur of S-nitrosothiols to form a mixed disulfide between the inactivator and papain.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Papain by S-Nitrosothiols

Xian

Chen

Liu

et al. 2000

Journal of Biological Chemistry

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“…This mechanism is responsible for destruction of viruses, fungi, bacteria and parasites (Colasanti et al 2002). The most important group of proteins affected by nitrosation is the cysteine containing proteins (cysteine proteases, cystein-rich aspases or ''caspases'', and capsid viral proteins) (Colasanti et al 2002;Torre et al 2002) a promise in target-cell based immunotherapies against malaria and viruses (Cao et al 2003;Izuhara et al 2008;Rosenthal et al 2002;Sharma et al 2004;Venturini et al 2000).…”

Section: Myeloperoxidase and No-induced Cysteine Disruption: Another mentioning

confidence: 99%

Oxidative and Nitrosative Stress on Phagocytes’ Function: from Effective Defense to Immunity Evasion Mechanisms

Ferrari

Souto

França

et al. 2011

Arch. Immunol. Ther. Exp.

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Although oxygen, nitrogen, and chlorine reactive species have been associated with disease pathogenesis, their partial absence is very harmful to the body's innate immune defense. Lacking of adequate release of free radicals from activated phagocytes is related to impaired ability on fungi, bacteria, and protozoa killing. We constructed an updated conceptual landmark regarding the paramount role of free radicals in phagocyte defense systems (phagocyte oxidase, myeloperoxidase, and nitric oxide/peroxynitrite system) on natural immunity. Diverse fungal, bacterial and protozoal pathogens evade the phagocytes' oxidative/nitrosative burst though antioxidant genes, enzymes and proteins. The most important evasion mechanisms were also described and discussed. These interconnected systems were reviewed and discussed on the basis of knowledge from relevant research groups around the globe. Phagocyte-derived free radicals are essential to destroy important human pathogens during the course of innate immunity.

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“…This dosedependent effect has been assigned to the nitrosylation of the Cys catalytic residue (Venturini et al, 2000a;Venturini et al, 2000b). Considering these antiparasitic effects of NO…”

Section: The Role Of Myoglobin During Parasite Infection Under Normoxmentioning

confidence: 99%

“…• by mediating chemical modifications of proteins, which is directly killing or decreasing parasite growth (Brunet, 2001;Venturini et al, 2000a;Venturini et al, 2000b), Ascenzi et al proposed that in this case the degradation of NO…”

Section: The Role Of Myoglobin During Parasite Infection Under Normoxmentioning

confidence: 99%

Unmasking the Janus face of myoglobin in health and disease

Hendgen‐Cotta

Flögel

Kelm

et al. 2010

Journal of Experimental Biology

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SummaryFor more than 100 years, myoglobin has been among the most extensively studied proteins. Since the first comprehensive review on myoglobin function as a dioxygen store by Millikan in 1939 and the discovery of its structure 50 years ago, multiple studies have extended our understanding of its occurrence, properties and functions. Beyond the two major roles, the storage and the facilitation of dioxygen diffusion, recent physiological studies have revealed that myoglobin acts as a potent scavenger of nitric oxide (NO • ) representing a control system that preserves mitochondrial respiration. In addition, myoglobin may also protect the heart against reactive oxygen species (ROS), and, under hypoxic conditions, deoxygenated myoglobin is able to reduce nitrite to NO • leading to a downregulation of the cardiac energy status and to a decreased heart injury after reoxygenation. Thus, by controlling the NO • bioavailability via scavenging or formation, myoglobin serves as part of a sensitive dioxygen sensory system. In this review, the physiological relevance of these recent findings are delineated for pathological states where NO • and ROS bioavailability are known to be critical determinants for the outcome of the disease, e.g. ischemia/reperfusion injury. Detrimental and beneficial effects of the presence of myoglobin are discussed for various states of tissue oxygen tension within the heart and skeletal muscle. Furthermore, the impact of myoglobin on parasite infection, rhabdomyolysis, hindlimb and liver ischemia, angiogenesis and tumor growth are considered.

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Nitric Oxide Inhibits Falcipain, the Plasmodium falciparum Trophozoite Cysteine Protease

Cited by 38 publications

References 33 publications

Inhibition of Papain by S-Nitrosothiols

Inhibition of Papain by S-Nitrosothiols

Oxidative and Nitrosative Stress on Phagocytes’ Function: from Effective Defense to Immunity Evasion Mechanisms

Unmasking the Janus face of myoglobin in health and disease

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