Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from Plasmodium falciparum

Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase us ed by Plasmondium falciparum to digest hemoglobin during the blood stage of malaria. A large shift between the N-domain and the central and C-domains of proplasmepsin II opens the active site deft, preventing the formation of a functional aspartic proteinase active site. This mode of inhibition of c atalytic activity has not been observed in any other aspartic proteinase zy mogen. Instead of occluding a pre-formed active site, as in the gastric asp artic proteinase zymogens, the prosegment of proplasmepsin II interacts ext ensively with the C-domain and serves as a 'harness' to keep the domains ap art. Disruption of key salt bridges at low pH may be important in activatio n.