2. Academic Validation
  3. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility

Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility

  • Nat Chem Biol. 2008 Jun;4(6):347-56. doi: 10.1038/nchembio.87.
Nobutaka Kato 1,  Tomoyo Sakata,  Ghislain Breton,  Karine G Le Roch,  Advait Nagle,  Carsten Andersen,  Badry Bursulaya,  Kerstin Henson,  Jeffrey Johnson,  Kota Arun Kumar,  Felix Marr,  Daniel Mason,  Case McNamara,  David Plouffe,  Vandana Ramachandran,  Muriel Spooner,  Tove Tuntland,  Yingyao Zhou,  Eric C Peters,  Arnab Chatterjee,  Peter G Schultz,  Gary E Ward,  Nathanael Gray,  Jeffrey Harper,  Elizabeth A Winzeler
Affiliations

Affiliation

  • 1 Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, ICND202 La Jolla, California 92037, USA.
PMID: 18454143 DOI: 10.1038/nchembio.87
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.

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