Malaria parasite Plasmodium falciparum completes its life cycle in vertebrate human and
invertebrate mosquito hosts. Inside the mosquito midgut, interaction between ookinete surfaceexpressed
P. falciparum enolase (PfENO) and host serine protease plasminogen obtained through
blood meal is essential for midgut invasion. Lysine motif on enolases is known to bind to plasminogen
through its kringle motifs. A PfENO lysine motif peptide has been shown to inhibit midgut invasion of
ookinetes and oocyst development but the region of interaction of plasminogen has not been identified.
In this study, attempts were made to identify the region of plasminogen involved in binding to
PfENO lysine motif. By protein-protein docking, the lysine motif was found to interact with kringle 4 of plasminogen.
Virtual screening based on plasminogen lysine motif binding residues identified a number of peptidomimetics. Molecular
docking revealed that the identified peptidomimetics docked on PfENO region containing the lysine motif and hence
could be potential blocker of this interaction. Blockade of this interaction could potentially block the development of oocysts
and parasite transmission.
Keywords: Malaria, Plasmodium falciparum, enolase, plasminogen, ookinete, transmission blocking.
Rights & PermissionsPrintExport