STRUCTURAL STUDIES OF TRYPANOSOMAL GLYCOLYTIC ENZYMES

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The parasitic trypanosomal species of the genera Trypanosoma and Leishmania are the causative agents of a wide variety of severely destructive diseases. One of the deadliest of these diseases is African sleeping sickness, the causative agent of which is Trypanosoma bruccei. Compounds which selectively inhibit trypanosomal glycolytic enzymes over the equivalent human glycolytic enzymes would be an excellent starting point for the design of new drugs effective in attentuating trypanosomal diseases. We propose to employ a cyclic process of three-dimensional structure determination and molecular modelling in the search for such compounds. This proposal concerns the structural determination aspect of the drug design cycle pertaining to two of these trypanosomal glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and aldolase.