Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase
| Autor: | Anna Oksman, R. Mueller, Daniel E. Goldberg, Ilya Y. Gluzman, A. Knickerbocker, Susan E. Francis, David G. Russell, M.L. Bryant, David R. Sherman |
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| Rok vydání: | 1994 |
| Předmět: |
Molecular Sequence Data
Plasmodium falciparum Plasmepsin Protozoan Proteins Cathepsin D Vacuole Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Antimalarials Hemoglobins Plasmepsin II Protein targeting parasitic diseases medicine Animals Aspartic Acid Endopeptidases Humans Amino Acid Sequence Cloning Molecular Microscopy Immunoelectron Molecular Biology General Immunology and Microbiology Base Sequence Sequence Homology Amino Acid General Neuroscience Dipeptides Exons DNA Protozoan biology.organism_classification Biochemistry Vacuoles Hemoglobin Plasmepsin I Research Article |
| Zdroj: | The EMBO journal. 13(2) |
| ISSN: | 0261-4189 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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