Targeting the plasmepsin 4 orthologs of Plasmodium sp. with "double drug" inhibitors.
Plasmepsin 4 (PM4) is a digestive vacuole enzyme found in all Plasmodium species examined to date. While P. falciparum has three additional aspartic proteinases in its digestive vacuole in addition to plasmepsin 4, other Plasmodium species have only PM4 in their digestive vacuole. Therefore, PM4 may be a good target for the development of an antimalarial drug. This study presents data obtained with PM4s from several Plasmodium species. Low nanomolar K(i) values have been observed for all PM4s studied.
Janka
Linda
L
Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610-0245, USA.
Clemente
Jose
J
Vaiana
N
N
Sparatore
A
A
Romeo
Sergio
S
Dunn
Ben M
BM
D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004792:Enzyme Precursors / Q000378:metabolism; D015870:Gene Expression; D002479:Inclusion Bodies; D008958:Models, Molecular; D010961:Plasmodium / Q000201:enzymology* / Q000235:genetics; D011319:Primaquine / Q000378:metabolism / Q000494:pharmacology; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D020673:Protein Renaturation; D015800:Protozoan Proteins / Q000302:isolation & purification; D014617:Vacuoles / Q000201:enzymology
D000596:Amino Acids; D000962:Antimalarials; D004792:Enzyme Precursors; D011480:Protease Inhibitors; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin; D011319:Primaquine; C013165:statine