Most enzymes of carbohydrate metabolism of T. brucei
and L. major have been cloned, sequenced,
overexpressed and characterised in our laboratory. Recently,
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK2/FBPase2)
and phosphofructokinase (PFK) were characterized and the
three-dimensional protein structures of PFK and pyruvate
kinase were solved in collabloration with Dr. L. Gilmore
(University of Edinburgh, UK) and their coworkers.
Based on the crystal structures so obtained, and on insight
in the kinetic properties and catalytic mechanisms, inhibitors
of each of these enzymes have been designed and synthesised
in collaboration with Prof. Casimir Blonski (Université
Paul Sabatier, Toulouse, France) and Prof. Malcolm Wilkinshaw
(University of Edinburg, Scotland).
We are also investigating glycosomal membrane proteins
that are thought to be involved in the transport of lipid
solutes across the membrane. Several such putative transporters
(TbGAT1 and 2) have already been cloned and sequenced. Investigation
of their subcellular localisation involves transfection
of trypanosomes with constructs encoding fusions of segments
of the transporters and fluorescent reporter proteins.
People involved in the subject:
-
Nathalie Chevalier
- Véronique Hannaert
-
Paul Michels
- Fred Opperdoes
- Muriel Mazet
uclouvain.be>