Thioredoxin reductase 1 (Trr1) from Saccharomyces cerevisiae is a member of the family of pyridine nucleotide-disulfide oxidoredutases capable to reduce redox active disulfide bond of the cytosolic thioredoxin1 (Trx1) and thioredoxin 2 (Trx2). NADPH, Trr1 and Trx1 (or Trx2) comprise the thioredoxin system, which is involved in several biological processes, including reduction of disulfide bonds and response to oxidative stress. Two types of thioredoxin reductases appeared during evolution. Both are homodimeric proteins and possess two domains: the NADPH and FAD binding domains. In prokaryotes, lower eukaryotes and plants each thioredoxin reductase subunit has a molecular weight of about 35000 Da. Thioredoxin reductases from mammalian organisms possess molecular weight of about 55000Da and the active site contains a selenocysteine. Moreover crystallographic studies have revealed that the location of NADPH and FAD binding domains differ significantly in these two enzyme types. Here, we described the  crystal structure of thioredoxin reductase from Saccharomyces cerevisiae at 2.4 Å resolution. The protein structure of Trr1 presents a disulfide between the catalytic cysteines with the FAD molecule near to the catalytic cysteines. Structural comparisons of domains organization reveal that Saccharomyces cerevisiae Trr1 resembles the lower eukaryotes and plants thioredoxin reductases. The protein topology implies that the Trr1 catalytic activity requires large structural modifications for the thioredoxin reduction. Molecular modeling studies imply that an intra subunit electron transfer accounts with very large domain rotation for the thioredoxins reduction. The domains reorganization reveals an extensive structural homology with other members of pyridine nucleotide-disulfide oxidoredutases family. Biochemical and structural analysis  of the yeast Trr1 provide insights concerning to the evolution and enzymatic mechanism of this protein towards cytosolic thioredoxins reduction (Financial Support: FAPESP).