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Content archived on 2024-06-16

Targetting malarial cell cycle kinases

Objective

Plasmodium falciparum cell cycle regulators are promising targets for novel anti-malarial drug design. This application is firmly based in the post-genomic era where the identification of novel drug targets is greatly facilitated by the availability of the P. falciparum genomic databases. P. falciparum cell cycle regulators are promising drug targets because of their predicted essential roles in regulating the pathogen's life-cycle. We have determined the structure of PfPK5. the first structure of a P. falciparum protein kinase and the first of a cyclin-dependent kinase (CDK) not derived from humans. A comparison of CDK structures from these two evolutionarily remote organisms suggests that the fold and the mechanism of inactivation of monomeric CDKs are highly conserved. The first aim of this project is to employ X-ray crystallographic studies to guide the development of potent and selective small molecule ATP-competitive inhibitors of P. falciparum protein kinase 5 (PfPK5), a member of the P. falciparum cyclin-dependent protein kinase family. Homologues of this enzyme in other eukaryotes play an essential role in regulating cell cycle progression. These compounds will be useful tools for P. falciparum cell cycle studies, and will provide lead compounds for anti-malarial drug development. The second aim of the project is to employ biochemical and biophysical methods to characterise CDK/cyclin complexes. This will explore the evolutionary conservation of the structural mechanisms that regulate the eukaryotic cell cycle. The final aim is to characterise P. falciparum cyclin 4 (Pfcyc-4) a novel member of the cyclin family that shows a distinct pattern of expression in the erythrocytic stages of the parasite's life cycle.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Topic(s)

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Call for proposal

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FP6-2002-MOBILITY-5
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
EU contribution
No data
Address
University Offices, Wellington Square
OXFORD
United Kingdom

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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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