Import of host $\delta$-aminolevulinate dehydratase into the malarial parasite: Identification of a new drug target

Bonday, ZQ and Dhanasekaran, S and Rangarajan, PN and Padmanaban, G (2000) Import of host $\delta$-aminolevulinate dehydratase into the malarial parasite: Identification of a new drug target. In: Nature Medicine, 6 (8). pp. 898-903.

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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 $(ALAD- \Delta NC)$ of the host erythrocyte ALAD was able to compete with the full-length enzyme for binding to the P. berghei membrane. $ALAD-\Delta NC$ 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.

Item Type:	Journal Article
Publication:	Nature Medicine
Publisher:	Nature Publishing Group
Additional Information:	Copyright of this article belongs to Nature Publishing Group.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	08 Oct 2007
Last Modified:	19 Sep 2010 04:40
URI:	http://eprints.iisc.ac.in/id/eprint/12150

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