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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-05-04

AUTHORS

Nobutaka Kato, 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

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. More... »

PAGES

347-356

Journal

TITLE

Nature Chemical Biology

ISSUE

6

VOLUME

4

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nchembio.87

DOI

http://dx.doi.org/10.1038/nchembio.87

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018037778

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18454143


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