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

D. E. Goldberg, A. F.G. Slater, R. Beavis, B. Chait, A. Cerami, G. B. Henderson

Research output: Contribution to journalArticle

223 Scopus citations

Abstract

Hemoglobin 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 hemoglobinolytic 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 α33Phe 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.

Original languageEnglish
Pages (from-to)961-969
Number of pages9
JournalJournal of Experimental Medicine
Volume173
Issue number4
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

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