STRUCTURAL BIOLOGY OF T. cruzi BROMODOMAIN FACTORS AS POTENTIAL TARGET FOR DRUG DESING

GÓMEZ BARROSO JA, JEREZ B, VILLANOVA V, SERRA E, AGUILAR CF.

Mendoza

Congreso; XXVI Annual Scientific Meeting of Cuyo Biology Society; 2008

Sociedad de Biología de Cuyo

STRUCTURAL BIOLOGY OF T. cruzi BROMODOMAIN FACTORS AS POTENTIAL TARGET FOR DRUG DESING Gómez Barroso JA, Jerez B, Villanova V, Serra E, Aguilar CF. Lab de Biol Mol Estructural, Univ Nac de San Luis, San Luis 5700. E-mail: jagomez@unsl.edu.ar Trypanosoma cruzi is the etiologic agent of Chagas’ disease. Th objective of our work is the resolution by X-ray crystallography o the three-dimensional structure of T. cruzi bromodomain facto proteins as a first step for rational drug design based on the structure The main objective of the Chagas´ Disease Research Network is th search for protein targets in metabolic routes absent in the human host and common in trypanosomatids. The T. cruzi proteins studied in this work are three bromodomain factors: TcBDF1, TcBDF2 and TcBDF3. They are expressed in E. coli as fusion proteins with N terminal His-tag. We have overexpressed, purified and solubilized these proteins for crystallization and other structural assays Refolding assays was realized by TcBFD3. We have carried ou bioinformatic studies. These proteins were overexpressed and purified in adequate amounts for crystallization assays and othe structural studies. Preliminary structural and bioinformatic studie revealed important properties which can be used for drug design.