Protein kinases of the human malaria parasite <it>Plasmodium falciparum</it>: the kinome of a divergent eukaryote

<p>Abstract</p> <p>Background</p> <p>Malaria, caused by the parasitic protist <it>Plasmodium falciparum</it>, represents a major public health problem in the developing world. The <it>P. falciparum </it>genome has been sequenced, which provides n...

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Bibliographic Details
Main Authors: Packer Jeremy, Equinet Leila, Ward Pauline, Doerig Christian
Format: Article
Language:English
Published: BMC 2004-10-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/5/79
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Summary:<p>Abstract</p> <p>Background</p> <p>Malaria, caused by the parasitic protist <it>Plasmodium falciparum</it>, represents a major public health problem in the developing world. The <it>P. falciparum </it>genome has been sequenced, which provides new opportunities for the identification of novel drug targets. Eukaryotic protein kinases (ePKs) form a large family of enzymes with crucial roles in most cellular processes; hence malarial ePKS represent potential drug targets. We report an exhaustive analysis of the <it>P. falciparum </it>genomic database (PlasmoDB) aimed at identifying and classifying all ePKs in this organism.</p> <p>Results</p> <p>Using a variety of bioinformatics tools, we identified 65 malarial ePK sequences and constructed a phylogenetic tree to position these sequences relative to the seven established ePK groups. Predominant features of the tree were: (i) that several malarial sequences did not cluster within any of the known ePK groups; (ii) that the CMGC group, whose members are usually involved in the control of cell proliferation, had the highest number of malarial ePKs; and (iii) that no malarial ePK clustered with the tyrosine kinase (TyrK) or STE groups, pointing to the absence of three-component MAPK modules in the parasite. A novel family of 20 ePK-related sequences was identified and called FIKK, on the basis of a conserved amino acid motif. The FIKK family seems restricted to Apicomplexa, with 20 members in <it>P. falciparum </it>and just one member in some other <it>Apicomplexan </it>species.</p> <p>Conclusion</p> <p>The considerable phylogenetic distance between Apicomplexa and other Eukaryotes is reflected by profound divergences between the kinome of malaria parasites and that of yeast or mammalian cells.</p>
ISSN:1471-2164