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As an experimental model we use the glycolytic enzyme triosephosphate isomerase. The three-dimensional structure and kinetic characteristics of the TPI of several species are known in detail. In mesophilic species, the active enzyme is a dimer made up of two identical subunits, where each subunit adopts the structure of a barrel consisting of eight alpha/beta units. Folding into the active dimer requires an intramolecular step in which the structureless monomers acquire a conformation that can recognize another monomer, and an intermolecular step in which the monomers are associated to form the biologically active structure.
Our particular interest is to determine and characterize the folding route of the TPI of two species: Trypanosoma brucei and Sacharomyces cereviseae. The three-dimensional structure of these enzymes is very similar. However, there are differences in the regions of the molecule that form the interface between the two monomers. Results obtained by our laboratory in collaboration with R. Zubillaga (UAM-I) show differences in the folding pattern of these enzymes. Our objective is to quantify, in energetic terms, the stability of the monomers and the dimer in order to correlate the differences in energy between the structures. With these studies, we expect to be able to understand the mechanism through which TPI adopts an active conformation.