Import of host delta-aminolevulinate dehydratase into the malarial parasite: identification of a new drug target |
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Authors: | Bonday Z Q Dhanasekaran S Rangarajan P N Padmanaban G |
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Institution: | Department of Biochemistry, Indian Institute of Science Bangalore: 560 012, India. |
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Abstract: | The parasite Plasmodium berghei imports the enzyme delta-aminolevulinate dehydratase (ALAD), and perhaps the subsequent enzymes of the pathway from the host red blood cell to sustain heme synthesis. Here we have studied the mechanism of this import. A 65-kDa protein on the P. berghei membrane specifically bound to mouse red blood cell ALAD, and a 93-amino-acid fragment (ALAD-DeltaNC) of the host erythrocyte ALAD was able to compete with the full-length enzyme for binding to the P. berghei membrane. ALAD-DeltaNC was taken up by the infected red blood cell when added to a culture of P. falciparum and this led to a substantial decrease in ALAD protein and enzyme activity and, subsequently, heme synthesis in the parasite, resulting in its death. |
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