Plasmepsin 4, the food vacuole aspartic proteinase found in all Plasmodium spp. infecting man.
Plasmepsins are aspartic proteinases of the malaria parasite, and seven groups of plasmepsins have been identified by comparing genomic sequence data available for the genes encoding these enzymes from Plasmodium falciparum, Plasmodium vivax, Plasmodium knowlesi, Plasmodium berghei, and Plasmodium yoelii. The food vacuole plasmepsins typified by plasmepsin 4 from P. falciparum (PfPM4) constitute one of these groups. Genes encoding the ortholog of PfPM4 have been cloned from Plasmodium ovale, Plasmodium malariae, and P. vivax. In addition, P. falciparum contains three paralagous food vacuole plasmepsins or plasmepsin-like enzymes that appear to have arisen by gene duplication, plasmepsins 1 (PfPM1), 2 (PfPM2) and HAP, and all four were localized to purified food vacuole preparations by two-dimensional gel electrophoresis and mass spectroscopic analysis. The three paralogs of PfPM4 do not have counterparts in the six other Plasmodium spp. examined by genomic DNA blot analysis and by review of available genomic sequence data. The presence of these paralogs among the food vacuole plasmepsins in P. falciparum as compared with the other three species causing malaria in man will impact efforts to rationally design antimalarials targeting the food vacuole plasmepsins.
Dame
John B
JB
Department of Pathobiology, College of Veterinary Medicine, University of Florida, Box 110880, Gainesville, FL 32611-0880, USA. damej@mail.vetmed.ufl.edu
Yowell
Charles A
CA
Omara-Opyene
Levi
L
Carlton
Jane M
JM
Cooper
Roland A
RA
Li
Tang
T
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008288:Malaria / Q000469:parasitology*; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000145:classification / Q000201:enzymology*; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014617:Vacuoles / Q000201:enzymology*
D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin