title: Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum.
abstract: Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase used by Plasmodiumfalciparum 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 cleft, preventing the formation of a functional aspartic proteinase active site. This mode of inhibition of catalytic activity has not been observed in any other aspartic proteinase zymogen. Instead of occluding a pre-formed active site, as in the gastric aspartic proteinase zymogens, the prosegment of proplasmepsin II interacts extensively with the C-domain and serves as a 'harness' to keep the domains apart. Disruption of key salt bridges at low pH may be important in activation.
authors.affiliation: Medical Research Council Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: N K
authors.initials: NK
authors.lastname: Bernstein
authors.forename: M M
authors.initials: MM
authors.lastname: Cherney
authors.forename: H
authors.initials: H
authors.lastname: Loetscher
authors.forename: R G
authors.initials: RG
authors.lastname: Ridley
authors.forename: M N
authors.initials: MN
authors.lastname: James
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004792:Enzyme Precursors / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry*; D011487:Protein Conformation; D015800:Protozoan Proteins; D017421:Sequence Analysis
chemical_list: D004792:Enzyme Precursors; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C116755:proplasmepsin II; C100637:plasmepsin II