Download plasmodium protein kinases: from database mining to the search for

PLASMODIUM PROTEIN KINASES: FROM DATABASE MINING TO THE SEARCH
FOR NOVEL ANTIMALARIALS
PROTÉINES KINASES DE PLASMODIUM: DE LA FOUILLE DES BANQUES DE
DONNÉES À LA RECHERCHE
DE NOUVEAUX ANTIPALUDÉENS
Pauline WARD1, Leila EQUINET1, Dominique DORIN1, Marie-Paule NIVEZ1, Luc REININGER1, Laurent
MEIJER2, Jeremy PACKER3 & Christian DOERIG 1
1 Inserm team, Wellcome Centre for Molecular Parasitology, University of Glasgow,
Glasgow, Scotland, UK; 2 The Rockefeller University, New York, USA / Station Biologique de Roscoff,
C.N.R.S., Bretagne, France; 3 Bioinformatics Group, Abbott Laboratories, Abbott Park IL 60064, USA
The complement of eukaryotic (ePK) protein kinase genes present in the Plasmodium
falciparum genome was investigated by systematic database mining, and a phylogenetic tree was
constructed to position the 65 malarial enzymes relative to the seven established groups of ePKs.
Predominant features of the tree were: (i) that several enzymes did not cluster strongly with any of the
known protein kinase groups; (ii) that among the seven ePK groups, the CMGC group, which includes
enzymes involved in the control of cell proliferation, had more malarial ePKs than any other group; (iii)
that no malarial PK clustered with the tyrosine kinase (TK) group; and (iv) that no members of the dualspecificity protein kinase (MAPKK) family (a subgroup of the STE group) are present in the P.
falciparum genome. In addition, a novel, apparently Plasmodium-specific family of 18 genes encoding
proteins with high homology to subdomains II to XI of the protein kinase catalytic domain has been
identified and called FIKK, on the basis of a conserved amino acid motif. Although no catalytic activity
has so far been demonstrated for any FIKK family member, the presence of all residues demonstrated
as essential for phosphotransfer in typical ePK suggests that these proteins may indeed function as
protein kinases.
The presentation of these findings will be complemented by data from our work on the
biochemical characterisation of malarial CMGC kinases and their potential use as drug targets.