title: Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine.
abstract: Hemoglobin degradation is a metabolic process that is central to the growth and maturation of the malaria parasite Plasmodium falciparum. Two aspartic proteases that initiate degradation, plasmepsins (PMs) I and II, have been identified and extensively characterized. Eight additional PM genes are present in the P. falciparum genome. To better understand the enzymology of hemoglobin degradation, it is necessary to determine which of these genes are expressed when hemoglobin degradation is occurring, which encode active enzymes, and which gene products are found in the food vacuole where catabolism takes place. Our genome-wide analysis reveals that PM I, II, and IV and histo-aspartic protease encode hemoglobin-degrading food vacuole proteases. Despite having a histidine in place of one of the catalytic aspartic acids conserved in other aspartic proteases, histo-aspartic protease is an active hydrolase.
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Box 8230, St. Louis, MO 63110, USA.
authors.forename: Ritu
authors.initials: R
authors.lastname: Banerjee
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Wandy
authors.initials: W
authors.lastname: Beatty
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pelosof
authors.forename: Michael
authors.initials: M
authors.lastname: Klemba
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Goldberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000201:enzymology
chemical_list: D006454:Hemoglobins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin; C100637:plasmepsin II