Objective
* To study the structure and kinetics of phosphofructokinase (PFK) and pyruvate kinase (PYK) of Leishmania, key enzymes in the metabolism of the parasite, and to determine differences with the corresponding mammalian enzymes.
* To design and synthesize selective inhibitors of the Leishmania enzymes, based on their differences with the mammallian enzymes.
Expected Outcome
* The primary structure of Leishmania PFK and PYK will become available.
* The enzymes will be overexpressed in a heterologous system and purified.
* Kinetic parameters of the enzymes will be established.
* Preliminary information on the structure of the enzymes will become available.
* Compounds with (some) inhibitory activity on the Leishmania enzymes will be synthesized.
* Cloning and sequence determination of the Leishmania PFK and PYK genes.
* Overexpression of the Leishmania enzymes in bacteria (Escherichia coli) or yeast (Hansenula polymorpha).
* Purification of the recombinant enzymes.
* Kinetic analysis of the purified enzymes.
* Structure modelling of the Leishmania enzymes, using the X-ray coordinates of the crystal structures of homologous enzymes.
* Structure-function analysis of residues potentially important for inhibitor design by site-directed mutagenesis.
* Crystallization trials of recombinant Leishmania PFK and PYK.
* Synthesis of potentially selective inhibitors of Leishmania PFK and PYK.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering crystals
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Coordinator
1200 BRUXELLES
Belgium
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.