Abstract
Intraerythrocytic Plasmodium falciparum digests vast amounts of hemoglobin within an acidic food vacuole (FV). Four homologous aspartic proteases participate in hemoglobin degradation within the FV. Plasmepsin (PM) I and II are thought to initiate degradation of the native hemoglobin molecule. PM IV and histo-aspartic protease (HAP) act on denatured globin further downstream in the pathway. PM I and II have been shown to be synthesized as zymogens and activated by proteolytic removal of a propiece. In this study, we have determined that the proteolytic processing of FV plasmepsins occurs immediately after a conserved Leu-Gly dipeptidyl motif with uniform kinetics and pH and inhibitor sensitivities. We have developed a cell-free in vitro processing assay that generates correctly processed plasmepsins. Our data suggest that proplasmepsin processing is not autocatalytic, but rather is mediated by a separate processing enzyme. This convertase requires acidic conditions and is blocked only by the calpain inhibitors, suggesting that it may be an atypical calpain-like protease.
Original language | English |
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Pages (from-to) | 157-165 |
Number of pages | 9 |
Journal | Molecular and Biochemical Parasitology |
Volume | 129 |
Issue number | 2 |
DOIs | |
State | Published - Jul 2003 |
Keywords
- Calpain
- Convertase
- Plasmepsin
- Protease