title: Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease.
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 alpha 33Phe 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.
authors.affiliation: Laboratory of Medical Biochemistry, Rockefeller University, New York, New York 10021.
authors.forename: D E
authors.initials: DE
authors.lastname: Goldberg
authors.forename: A F
authors.initials: AF
authors.lastname: Slater
authors.forename: R
authors.initials: R
authors.lastname: Beavis
authors.forename: B
authors.initials: B
authors.lastname: Chait
authors.forename: A
authors.initials: A
authors.lastname: Cerami
authors.forename: G B
authors.initials: GB
authors.lastname: Henderson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008288:Malaria / Q000097:blood*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D010963:Plasmodium falciparum / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D006454:Hemoglobins; D010446:Peptide Fragments; D016282:Aspartic Acid Endopeptidases