STRUCTURAL BIOLOGY OF T. cruzi ENERGETIC METABOLISM PROTEINS AS POTENTIAL TARGET FOR DRUG DESING

GÓMEZ BARROSO JA, MIRANDA M, STRADELLA F, BOUVIER LA, CANEPA GE, PEREIRA C, AGUILAR CF.

Mendoza

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

Sociedad de Biología de Cuyo

STRUCTURAL BIOLOGY OF T. cruzi ENERGETIC METABOLISM PROTEINS AS POTENTIAL TARGET FOR DRUG DESING Gómez Barroso JA, Miranda M, Stradella F, Bouvier LA, Canepa GE, Pereira C, Aguilar CF. Lab de Biol Mol Estructural, Univ Nac de San Luis. E-mail: jagomez@unsl.edu.ar Trypanosoma cruzi is the etiologic agent of Chagas’ disease. The objective of our work is the resolution by X-ray crystallography of the three-dimensional structure of T. cruzi proteins involved in energetic metabolism as a first step for rational drug design based on the structure. The main objective of the Chagas´ Disease Research Network is the 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: TcNDPK (Nucleoside Diphosphate Kinase), TcTAF9 (TATA Binding Factor 9) and TcAdK1 (Adenilate Kinase 1). 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. We have carried out bioinformatic studies. TcNDPK was studied in different cristalization conditions. TcNDPK crystals were used by X-ray diffraction assays. TcTAF9 was overexpressed, and solubilized in adequate quality for crystallization assays and other structural studies. Cristallization screenings were realized for TcAdK1. The structural particularities of these proteins showed a high potential for drug design.