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. 1987 Sep 1;166(3):816–821. doi: 10.1084/jem.166.3.816

Identification of three stage-specific proteinases of Plasmodium falciparum

PMCID: PMC2188684  PMID: 3305763

Abstract

We have identified and characterized three stage-specific proteinases of Plasmodium falciparum that are active at neutral pH. We analyzed ring-, trophozoite-, schizont-, and merozoite-stage parasites by gelatin substrate PAGE and characterized the identified proteinases with class-specific proteinase inhibitors. No proteinase activity was detected with rings. Trophozoites had a 28 kD proteinase that was inhibited by inhibitors of cysteine proteinases. Mature schizonts had a 35-40 kD proteinase that also was inhibited by cysteine proteinase inhibitors. Merozoite fractions had a 75 kD proteinase that was inhibited by serine proteinase inhibitors. The stage-specific activity of these proteinases and the correlation between the effects of proteinase inhibitors on the isolated enzymes with the effects of the inhibitors on whole parasites suggest potential critical functions for these proteinases in the life cycle of malaria parasites.

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Selected References

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  1. Beutler E., West C., Blume K. G. The removal of leukocytes and platelets from whole blood. J Lab Clin Med. 1976 Aug;88(2):328–333. [PubMed] [Google Scholar]
  2. David P. H., Hadley T. J., Aikawa M., Miller L. H. Processing of a major parasite surface glycoprotein during the ultimate stages of differentiation in Plasmodium knowlesi. Mol Biochem Parasitol. 1984 Apr;11:267–282. doi: 10.1016/0166-6851(84)90071-9. [DOI] [PubMed] [Google Scholar]
  3. Gyang F. N., Poole B., Trager W. Peptidases from Plasmodium falciparum cultured in vitro. Mol Biochem Parasitol. 1982 Apr;5(4):263–273. doi: 10.1016/0166-6851(82)90034-2. [DOI] [PubMed] [Google Scholar]
  4. Hadley T., Aikawa M., Miller L. H. Plasmodium knowlesi: studies on invasion of rhesus erythrocytes by merozoites in the presence of protease inhibitors. Exp Parasitol. 1983 Jun;55(3):306–311. doi: 10.1016/0014-4894(83)90027-9. [DOI] [PubMed] [Google Scholar]
  5. Heussen C., Dowdle E. B. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem. 1980 Feb;102(1):196–202. doi: 10.1016/0003-2697(80)90338-3. [DOI] [PubMed] [Google Scholar]
  6. Holder A. A., Freeman R. R. Biosynthesis and processing of a Plasmodium falciparum schizont antigen recognized by immune serum and a monoclonal antibody. J Exp Med. 1982 Nov 1;156(5):1528–1538. doi: 10.1084/jem.156.5.1528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jensen J. B. Concentration from continuous culture of erythrocytes infected with trophozoites and schizonts of Plasmodium falciparum. Am J Trop Med Hyg. 1978 Nov;27(6):1274–1276. doi: 10.4269/ajtmh.1978.27.1274. [DOI] [PubMed] [Google Scholar]
  8. Krogstad D. J., Schlesinger P. H., Gluzman I. Y. Antimalarials increase vesicle pH in Plasmodium falciparum. J Cell Biol. 1985 Dec;101(6):2302–2309. doi: 10.1083/jcb.101.6.2302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lambros C., Vanderberg J. P. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol. 1979 Jun;65(3):418–420. [PubMed] [Google Scholar]
  10. Lyon J. A., Haynes J. D. Plasmodium falciparum antigens synthesized by schizonts and stabilized at the merozoite surface when schizonts mature in the presence of protease inhibitors. J Immunol. 1986 Mar 15;136(6):2245–2251. [PubMed] [Google Scholar]
  11. Miller L. H., Hudson D., Rener J., Taylor D., Hadley T. J., Zilberstein D. A monoclonal antibody to rhesus erythrocyte band 3 inhibits invasion by malaria (Plasmodium knowlesi) merozoites. J Clin Invest. 1983 Oct;72(4):1357–1364. doi: 10.1172/JCI111092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schrével J., Bernard F., Maintier C., Mayer R., Monsigny M. Detection and characterization of a selective endopeptidase from Plasmodium berghei by using fluorogenic peptidyl substrates. Biochem Biophys Res Commun. 1984 Nov 14;124(3):703–710. doi: 10.1016/0006-291x(84)91015-5. [DOI] [PubMed] [Google Scholar]
  13. Sherman I. W. Biochemistry of Plasmodium (malarial parasites). Microbiol Rev. 1979 Dec;43(4):453–495. doi: 10.1128/mr.43.4.453-495.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sherman I. W., Tanigoshi L. Purification of Plasmodium lophurae cathepsin D and its effects on erythrocyte membrane proteins. Mol Biochem Parasitol. 1983 Jul;8(3):207–226. doi: 10.1016/0166-6851(83)90044-0. [DOI] [PubMed] [Google Scholar]
  15. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  16. Vander Jagt D. L., Hunsaker L. A., Campos N. M. Characterization of a hemoglobin-degrading, low molecular weight protease from Plasmodium falciparum. Mol Biochem Parasitol. 1986 Mar;18(3):389–400. doi: 10.1016/0166-6851(86)90095-2. [DOI] [PubMed] [Google Scholar]
  17. Yayon A., Cabantchik Z. I., Ginsburg H. Susceptibility of human malaria parasites to chloroquine is pH dependent. Proc Natl Acad Sci U S A. 1985 May;82(9):2784–2788. doi: 10.1073/pnas.82.9.2784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yayon A., Timberg R., Friedman S., Ginsburg H. Effects of chloroquine on the feeding mechanism of the intraerythrocytic human malarial parasite Plasmodium falciparum. J Protozool. 1984 Aug;31(3):367–372. doi: 10.1111/j.1550-7408.1984.tb02981.x. [DOI] [PubMed] [Google Scholar]

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