Study of a Unusual Methionine Sulfoxide Reductase from Trypanosoma cruzi

M.S. CABEZA; D.G. ARIAS; A.A. IGLESIAS; S.A. GUERRERO

Puerto Madryn

Congreso; XLVI Reunión Anual de SAIB; 2010

SAIB

STUDY OF AN UNUSUAL METHIONINE SULFOXIDE REDUCTASE FROM Trypanosoma cruzi 1 1 2 1 Cabeza MS , Arias DG , Iglesias AA , Guerrero SA 1 2 Lab. Bioquímica Microbiana ( IAL; UNL-CONICET). Lab. Enzimología Molecular (IAL; UNL-CONICET). E-mail:matiascabeza@gmail.com Trypanosomatids parasitize a wide variety of invertebrate and vertebrate hosts. Many efforts has been made to understand the mechanisms by which these organisms neutralize reactive species (RS) but much less is know about the proteins responsible of repairing the damage created byRS. Methionine sulfoxide reductases (Msrs) catalyze thiol-dependent reduction of oxidized methionine. MsrAand MsrB are the best know Msrs that repair methionine-S-sulfoxide and methionine-Rsulfoxide respectively. In addition, an Escherichia coli enzyme specific for free methionine-R-sulfoxide (fMsr) was recently discovered. This protein is present in some prokaryotes and unicellular eukaryotes. We find two orthologs in the genome of Trypanosoma cruzi. These proteins contain an extra C-terminal domain with a possible function in the regulation of type 2Aphosphatases. In this work, we carried out the cloning, purification and characterization of the fMsr N-terminal domains of both alleles. They reduce methionine-R-sulfoxide utilizing tryparedoxin as electron donor. The catalytic efficiency of the two alleles differs in one order of magnitude. This discrepancy could be explained on basis to the quaternary structure as we can realize by gel filtration assays. Efforts are being made to obtain the complete protein to understand the functional relationship between these domain fusions.