1. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility.
- Author
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Kato, Nobutaka, Sakata, Tomoyo, Breton, Ghislain, Le Roch, Karine G., Nagle, Advait, Andersen, Carsten, Bursulaya, Badry, Henson, Kerstin, Johnson, Jeffrey, Kumar, Kota Arun, Marr, Felix, Mason, Daniel, McNamara, Case, Plouffe, David, Ramachandran, Vandana, Spooner, Muriel, Tuntland, Tove, Zhou, Yingyao, Peters, Eric C., and Chatterjee, Arnab
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GENE expression , *PROTEIN kinases , *PLASMODIUM falciparum , *PARASITES , *CYTOKINESIS , *TOXOPLASMA gondii - Abstract
Calcium-dependent protein kinases play a crucial role in intracellular calcium signaling in plants, some algae and protozoa. In Plasmodium falciparum, calcium-dependent protein kinase 1 (PfCDPK1) is expressed during schizogony in the erythrocytic stage as well as in the sporozoite stage. It is coexpressed with genes that encode the parasite motor complex, a cellular component required for parasite invasion of host cells, parasite motility and potentially cytokinesis. A targeted gene-disruption approach demonstrated that pfcdpk1 seems to be essential for parasite viability. An in vitro biochemical screen using recombinant PfCDPK1 against a library of 20,000 compounds resulted in the identification of a series of structurally related 2,6,9-trisubstituted purines. Compound treatment caused sudden developmental arrest at the late schizont stage in P. falciparum and a large reduction in intracellular parasites in Toxoplasma gondii, which suggests a possible role for PfCDPK1 in regulation of parasite motility during egress and invasion. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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