Waters, N. C., Kopydlowski, K. M., Guszczynski, T., Wei, L., Sellers, P., Ferlan, J. T., Lee, P. J., Li, Z., Woodard, C. L., Shallom, S., Gardner, M. J., Prigge, S. T.
Functional Characterization of the Acyl Carrier Protein (PfACP) and Beta-ketoacyl ACP Synthase III (PfKASIII) from Plasmodium falciparum
Mol Biochem Parasitol. 2002 Aug 28; 123(2): 85-94.
The genome of the malaria parasite, Plasmodium falciparum, appears to contain the proteins necessary for a Type II dissociated fatty acid biosynthetic system. Here we report the functional characterization of two proteins from this system. Purified recombinant acyl carrier protein (ACP) and beta-ketoacyl-ACP synthase III (KASIII) from P. falciparum are soluble and active in a truncated form. Malarial ACP is activated by the addition of a 4'-phosphopantetheine prosthetic group derived from coenzyme A, generating holo-PfACP. Holo-PfACP is an effective substrate for the transacylase activity of PfKASIII, but substitution of a key active site cysteine in PfKASIII to alanine or serine abolishes enzymatic activity. During the schizont stage of parasite development, there is a significant up-regulation of the mRNAs corresponding to these proteins, indicating an important metabolic requirement for fatty acids during this stage.