A three-dimensional structure of histo-aspartic protease (HAP), a pepsin-like 
enzyme from the causative agent of malaria Plasmodium falciparum, is suggested 
on the basis of homologous modeling followed by equilibration by the method of 
molecular dynamics. The presence of a His residue in the catalytic site instead 
of an Asp residue, which is characteristic of pepsin-like enzymes, and 
replacement of some other conserved residues in the active site make it possible 
for the enzyme to function by the covalent mechanism inherent in serine 
proteases. The detailed structures of HAP complexes with pepstatin, a 
noncovalent inhibitor of aspartic proteases, and phenylmethylsulfonyl fluoride, 
a covalent inhibitor of serine proteases, as well as with a pentapeptide 
substrate are discussed.