ABSTRACT
An inventory of the structural information waiting to be exploited by structure-based drug design reveals eight potential target enzymes. Since for most trypanosomatid proteins there is a human counterpart it is mandatory that designed inhibitors be selective, have very little affinity for the equivalent enzymes of the human host. In the bloodstream of the human host, trypanosomes are metabolically "lazy". Since there is plenty of glucose and oxygen available, they rely solely on glycolysis to the stage of pyruvate for their energy supply. In trypanosomes, seven enzymes involved in glycolysis, from hexokinase to phosphoglycerate kinase, are sequestered in specialized organelles, called glycosomes. If glycolysis could be blocked selectively, without affecting the equivalent enzymes of the host, one might have a promising therapy against trypanosomiasis. Triosephosphate Isomerase is a homodimeric enzyme that interconverts dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. It ensures that both trioses derived from glucose can be used for ATP production in the glycolytic pathway.
