Iron superoxide dismutases in eukaryotic pathogens: new insights from Apicomplexa andTrypanosomastructures

Abstract

Prior studies have highlighted the potential of superoxide dismutases as drug targets in eukaryotic pathogens. This report presents the structures of three iron-dependent superoxide dismutases (FeSODs) fromTrypanosoma cruzi,Leishmania majorandBabesia bovis. Comparison with existing structures fromPlasmodiumand other trypanosome isoforms shows a very conserved overall fold with subtle differences. In particular, structural data suggest thatB. bovisFeSOD may display similar resistance to peroxynitrite-mediated inactivationviaan intramolecular electron-transfer pathway as previously described inT. cruziFeSOD isoform B, thus providing valuable information for structure-based drug design. Furthermore, lysine-acetylation results inT. cruziindicate that acetylation occurs at a position close to that responsible for the regulation of acetylation-mediated activity in the human enzyme.