Structural highlights
Function
PLM2_PLAFX During the asexual blood stage, participates in initial cleavage of native host hemoglobin (Hb) resulting in Hb denaturation (PubMed:11782538, PubMed:15574427, PubMed:8844673). May cleave preferentially denatured hemoglobin that has been cleaved by PMI (PubMed:8844673). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum.,Bernstein NK, Cherney MM, Loetscher H, Ridley RG, James MN Nat Struct Biol. 1999 Jan;6(1):32-7. PMID:9886289[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Banerjee R, Liu J, Beatty W, Pelosof L, Klemba M, Goldberg DE. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):990-5. doi: 10.1073/pnas.022630099., Epub 2002 Jan 8. PMID:11782538 doi:http://dx.doi.org/10.1073/pnas.022630099
- ↑ Istvan ES, Goldberg DE. Distal substrate interactions enhance plasmepsin activity. J Biol Chem. 2005 Feb 25;280(8):6890-6. doi: 10.1074/jbc.M412086200. Epub 2004, Dec 1. PMID:15574427 doi:http://dx.doi.org/10.1074/jbc.M412086200
- ↑ Luker KE, Francis SE, Gluzman IY, Goldberg DE. Kinetic analysis of plasmepsins I and II aspartic proteases of the Plasmodium falciparum digestive vacuole. Mol Biochem Parasitol. 1996 Jul;79(1):71-8. doi: 10.1016/0166-6851(96)02651-5. PMID:8844673 doi:http://dx.doi.org/10.1016/0166-6851(96)02651-5
- ↑ Bernstein NK, Cherney MM, Loetscher H, Ridley RG, James MN. Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum. Nat Struct Biol. 1999 Jan;6(1):32-7. PMID:9886289 doi:10.1038/4905
