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 su bstrates and the interaction of synthetic inhibitors with recombinant and n aturally-occurring forms of plasmepsin II. In contrast, recombinant plasmep sin I was extended by 12 residues at its N-terminus relative to its natural ly-occurring counterpart and a 3-10-fold diminution in the k(cat) values wa s measured for substrate hydrolysis by the recombinant protein. However, co mparable K-i values were derived for the interaction of two distinct inhibi tors with both forms of plasmepsin I, thereby validating the use of recombi nant material for drug screening. The value of plasmepsin I inhibitors was determined by assessing their selectivity using human aspartic proteinases. (C) 1999 Federation of European Biochemical Societies.