This award will support Professor Mario Amzel of the Johns Hopkins University in a research collaboration with Professor Julio Urbina of the Universidad Central de Venezuela. The investigators intend to study the detailed molecular mechanisms of the phosphofructokinase (PFK) and the PEP-carboxylase kinase (PEP-CK) enzymes involved in the energy metabolism of the Trypanosoma Cruzi parasite. This parasite, endemic to most areas of Latin America and the Caribbean, infects animals and humans and in the latter it causes Chagas - a fatal disease that results in loss of heart function. The kinetic and regulatory properties of the two enzymes mentioned above play a central role in the unusual metabolic strategy of this protozoan parasite. Further understanding of these key enzymes will require knowledge of their three-dimensional structure. Using X-ray diffraction techniques, the investigators intend to gain some insight into their atomic structure. The study will serve to bring together the complementary strengths of the U.S. side in X-ray diffraction studies of energy metabolizing enzymes, with the expertise of the Venezuelan side in parasite metabolism. Knowledge of the three- dimensional structure of any of these enzymes will allow the design of more powerful agents against the parasite.
