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Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase.
Author(s) -
Francis S.E.,
Gluzman I.Y.,
Oksman A.,
Knickerbocker A.,
Mueller R.,
Bryant M.L.,
Sherman D.R.,
Russell D.G.,
Goldberg D.E.
Publication year - 1994
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1994.tb06263.x
Subject(s) - biology , plasmodium falciparum , aspartic acid , plasmodium (life cycle) , genetics , biochemistry , malaria , amino acid , parasite hosting , immunology , world wide web , computer science
Intraerythrocytic malaria parasites rapidly degrade virtually all of the host cell hemoglobin. We have cloned the gene for an aspartic hemoglobinase that initiates the hemoglobin degradation pathway in Plasmodium falciparum. It encodes a protein with 35% homology to human renin and cathepsin D, but has an unusually long pro‐piece that includes a putative membrane spanning anchor. Immunolocalization studies place the enzyme in the digestive vacuole and throughout the hemoglobin ingestion pathway, suggesting an unusual protein targeting route. A peptidomimetic inhibitor selectively blocks the aspartic hemoglobinase, prevents hemoglobin degradation and kills the organism. We conclude that Plasmodium hemoglobin catabolism is a prime target for antimalarial chemotherapy and have identified a lead compound towards this goal.