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: N K Bernstein, M M Cherney, H Loetscher, R G Ridley, M N James
• Journal: Nature structural biology (Nat Struct Biol) Vol. 6 Issue 1 Pg. 32-7 (Jan 1999) ISSN: 1072-8368 [Print] United States
• PMID: 9886289 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Precursors
• Protozoan Proteins
• Aspartic Acid Endopeptidases
• proplasmepsin II
• plasmepsin II

Topics

• Amino Acid Sequence
• Animals
• Aspartic Acid Endopeptidases (chemistry, genetics)
• Crystallography, X-Ray
• Enzyme Precursors (chemistry, genetics)
• Molecular Sequence Data
• Plasmodium falciparum (chemistry)
• Protein Conformation
• Protozoan Proteins
• Sequence Analysis