Trypanosoma cruzi PLA2: Initial characterization of enzyme-substrate interaction of a novel-old enzyme

S. COSSY ISASI; C.A. CONDAT

Sierra de la Ventana

Congreso; XLIII Reunión Anual SAB 2014; 2014

Sociedad Argentina de Biofísica

The fight against Chagas disease has been developed with different perspectives, one of which is the study of the metabolism of the parasite Trypanosoma cruzi and in particular the interactions enzyme-substrate in order to find drug targets needed to eliminate the parasite without commitment of the host. In this paper we analyze the interaction of PLA2 enzyme substrate whose structure was obtained by homology modeling. The gene was identified from the presence of the amino acids constituting the active site, the triad HIS, SER, ASP (GLU) that are responsible for the nucleophilic attack on the carbonyl atom of the ester carbon bond, belonging to the group of platelet- activating factor acetylhydrolases. The binding was originally studied by LInear Interaction Energies. The monomeric complexes (PAF or DPPC as ligands) were obtained with the PatchDock program. Simulations of bounded and dissociated states with implicit solvent (GBIS) were developed with NAMD. Results were visualized with VMD and Chimera. The electrostatic contribution increases approx 20kcal/mol in the bound state but VdW interactions decrease 28kcal/mol rendering the favorable terminus for the bound state.