[Modeling of substrate and inhibitory complexes of histidine-aspartic protease].
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.
Popov
M E
ME
Sten'gach
M A
MA
Andreeva
N S
NS
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D010963:Plasmodium falciparum / Q000201:enzymology*; D015800:Protozoan Proteins; D016415:Sequence Alignment
D009842:Oligopeptides; D015800:Protozoan Proteins; D006639:Histidine; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II