Plasmodium falciparum, P. vivax, and P. malariae: a comparison of the active site properties of plasmepsins cloned and expressed from three different species of the malaria parasite.
Aspartic endopeptidases (plasmepsins) have been implicated in the degradation of hemoglobin in the erythrocytic stage of infection by Plasmodium falciparum. To develop new targets for drug development, these enzymes have been isolated and cloned, expressed, and studied structurally and enzymatically. This study expands this approach to two other species of the malarial parasite, P. vivax and P. malariae. Expression of cloned genes from these species, utilizing methodology similar to that employed in the original reports on the enzymes from P. falciparum, has provided active enzymes for analysis by kinetic methods. We describe here studies of three enzymes, plasmepsin II from P. falciparum, and one plasmepsin from both P. vivax and P. malariae, utilizing oligopeptide substrates and low-molecular-weight inhibitors. These analyses provide new information on the properties of distinct regions of the active site cleft; such data can suggest strategies for drug design to inhibit these critical enzymes of the parasite.
Westling
J
J
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville 32610, USA.
Yowell
C A
CA
Majer
P
P
Erickson
J W
JW
Dame
J B
JB
Dunn
B M
BM
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D010965:Plasmodium malariae / Q000201:enzymology*; D010966:Plasmodium vivax / Q000201:enzymology*; D011480:Protease Inhibitors; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013045:Species Specificity; D013379:Substrate Specificity
D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin