Study of unusual methionine sulfoxide reductase from Trypanosoma cruzi.

CABEZA, MATÍAS S.; ARIAS, DIEGO G.; IGLESIAS, ALBERTO A.; GUERRERO, SERGIO A.

Congreso; SAIB XLVI Reunión Anual.; 2010

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 by RS.Methionine sulfoxide reductases (Msrs) catalyze thiol-dependent reduction of oxidized methionine. MsrA and 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 andunicellular eukaryotes. We find two orthologs in the genome of Trypanosoma cruzi. Theseproteins contain an extra C-terminal domain with a possible function in the regulation of type 2A phosphatases. 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 aselectron 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 understandthe functional relationship between these domain fusions.