Naturally-occurring and recombinant forms of the aspartic proteinases plasmepsins I and II from the human malaria parasite Plasmodium falciparum.
Comparable kinetic parameters were derived for the hydrolysis of peptide substrates and the interaction of synthetic inhibitors with recombinant and naturally-occurring forms of plasmepsin II. In contrast, recombinant plasmepsin I was extended by 12 residues at its N-terminus relative to its naturally-occurring counterpart and a 3-10-fold diminution in the k(cat) values was measured for substrate hydrolysis by the recombinant protein. However, comparable Ki values were derived for the interaction of two distinct inhibitors with both forms of plasmepsin I, thereby validating the use of recombinant material for drug screening. The value of plasmepsin I inhibitors was determined by assessing their selectivity using human aspartic proteinases.
Tyas
L
L
Cardiff School of Biosciences, Cardiff University, UK.
Gluzman
I
I
Moon
R P
RP
Rupp
K
K
Westling
J
J
Ridley
R G
RG
Kay
J
J
Goldberg
D E
DE
Berry
C
C
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000201:enzymology*; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D015800:Protozoan Proteins; D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin; C100637:plasmepsin II