Kinetic analysis of plasmepsins i and II, aspartic proteases of the plasmodium falciparum digestive vacuole

Kathryn E. Luker, Susan E. Francis, Ilya Y. Gluzman, Daniel E. Goldberg

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Plasmepsins I and II are Plasmodium falciparum aspartic proteases implicated in hemoglobin degradation. Using a synthetic fluorogenic peptide substrate based on the initial hemoglobin cleavage site, we have analyzed kinetic parameters of the two enzymes in native and recombinant forms. Both native plasmepsins cleave the model substrate well. Recombinant plasmepsin II behaves similarly to native enzyme, substantiating its usefulness for inhibition and structural studies. In contrast, recombinant plasmepsin I does not resemble its native homolog kinetically. A hybrid molecule, in which the polyproline loop of plasmepsin I has been replaced by the homologous sequence from plasmepsin II, still maintains the specificity/kinetics of plasmepsin II. This suggests that the polyproline loop, important for substrate recognition in the mammalian aspartic protease renin, does not play a similar role in the plasmepsins.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalMolecular and Biochemical Parasitology
Volume79
Issue number1
DOIs
StatePublished - Jul 1996

Keywords

  • Hemoglobin
  • Malaria
  • Polyproline loop
  • Proteolysis

Fingerprint

Dive into the research topics of 'Kinetic analysis of plasmepsins i and II, aspartic proteases of the plasmodium falciparum digestive vacuole'. Together they form a unique fingerprint.

Cite this