Acid Protease Activity in Plasmodium falciparum and P. knowlesi and Ghosts of Their Respective Host Red Cells

Lévy, Michael; Siddiqui, Wasim A.; Chou, S.C.

doi:10.1038/247546a0

Cited by 50 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As hemoglobin-laden endocytic vesicles mature, they not only lose their inner membranes, they become acidic (Yayon et al, 1984a;Krogstad et al, 1985) and acquire proteolytic enzymes (Levy et al, 1974;Vander Jagt et al, 1987;Goldberg et al, 1990;Kolakovich et al, 1997;Rosenthal, 2002;Banerjee et al, 2002); their cargo of hemoglobin is denatured (Yamada and Sherman, 1979;Goldie et al, 1990) and degraded (Goldberg et al, 1990;Kolakovich et al, 1997;Rosenthal, 2002;Banerjee et al, 2002); and peptides and FP are released. The peptides are degraded to amino acids (Moulder and Evans, 1946;Groman, 1951;Krugliak et al, 2002), probably by cytoplasmic proteases (Kolakovich et al, 1997).…”

Section: Production Of Ferriprotoporphyrin IXmentioning

confidence: 98%

Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs

2004

View full text Add to dashboard Cite

Section: Production Of Ferriprotoporphyrin IXmentioning

confidence: 98%

Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs

2004

View full text Add to dashboard Cite

“…By using native or denatured hemoglobin, cathepsin Dlike proteases were identified in 1). berghei [43,44], P. falciparum [24,45], P. knowlesi [32,45], and P. yoelii [2], and an acid low molecular weight protease from P. falciparum was also characterized [72].…”

Section: Introductionmentioning

confidence: 99%

Neutral proteases involved in the reinvasion of erythrocytes by Plasmodium merozoites

Schrével

Grellier

Mayer

et al. 1988

Biology of the Cell

View full text Add to dashboard Cite

Neutral proteases of Plasmodium sp erythrocytic stages were studied by means of a sensitive fluorogenic method and gelatin-SDS-PAGE. The substrates gluconoyl-Val-Leu-Gly-Lys(or Arg)-3-amido-9-ethylcarbazole were selectively hydrolyzed by an endopeptidase from rodent Plasmodium berghei (Pb) and Plasmodium chabaudi (Pc) and from human Plasmodium falciparum (Pf) parasites. These endopeptidases were purified from 100,000-g soluble schizont extract by high pressure liquid chromatography; they have a similar Mr of 68,000 in SDS-PAGE, and an optimal activity at pH 7.4. The Pb 68 and Pf 68 endopeptidases were localized in schizonts and also in merozoites as shown by indirect immunofluorescence on Pb merozoites and by the identification of the Pf 68 endopeptidase activity in free viable merozoites. The Pb 68 and Pf 68 endopeptidases belong to the class of cysteine proteases. Analysis by gelatin-SDS-PAGE of a Pb 68 endopeptidase-enriched fraction showed a reproducible 95,000 proteolytic band. The initial extracts showed a similar 95,000 proteolytic band, and also 2 other 90,000 and 85,000 major bands. During reinvasion experiments, it was possible to recover a 95,000 and a 40,000 protease band from supernates of cultures grown in a semidefined medium without serum. Hydrophilic peptide derivatives related to the substrate of Pf 68 endopeptidase are shown to be potential inhibitors of the Pf reinvasion process in vitro.

show abstract

“…To account for this enormous amount of protein breakdown that occurs in just a few hours of the parasite's trophozoite stage, we have proposed that there is an efficient and specific pathway for hemoglobin proteolysis in the digestive vacuole (16). Several putative malaria hemoglobinases have been described (17)(18)(19)(20)(21)(22)(23)(24)(25)(26), but it has been difficult to ascribe a physiological role in hemoglobinolysis to any of these activities. We have recently reported the purification and characterization ofPlasmodium falciparum digestive vacuoles in which the degradation ofhemoglobin occurs (16).…”

mentioning

confidence: 99%

Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease.

Goldberg

Slater

Beavis

et al. 1991

The Journal of Experimental Medicine

243

120

View full text Add to dashboard Cite

SummaryHemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole . Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolysic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between tx33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases . Isolated digestive vacuoles make a pepstatin-inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated.

show abstract

Acid Protease Activity in Plasmodium falciparum and P. knowlesi and Ghosts of Their Respective Host Red Cells

Cited by 50 publications

References 25 publications

Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs

Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs

Neutral proteases involved in the reinvasion of erythrocytes by Plasmodium merozoites

Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease.

Contact Info

Product

Resources

About