1. Iron superoxide dismutases in eukaryotic pathogens: new insights from Apicomplexa and Trypanosoma structures.
- Author
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Phan IQ, Davies DR, Moretti NS, Shanmugam D, Cestari I, Anupama A, Fairman JW, Edwards TE, Stuart K, Schenkman S, and Myler PJ
- Subjects
- Amino Acid Sequence, Apicomplexa chemistry, Apicomplexa enzymology, Apicomplexa genetics, Babesia bovis chemistry, Babesia bovis genetics, Crystallization, Crystallography, X-Ray, Eukaryota chemistry, Eukaryota genetics, Humans, Leishmania major chemistry, Leishmania major genetics, Molecular Sequence Data, Protein Structure, Secondary, Protein Structure, Tertiary, Superoxide Dismutase genetics, Trypanosoma cruzi chemistry, Trypanosoma cruzi genetics, Babesia bovis enzymology, Eukaryota enzymology, Leishmania major enzymology, Superoxide Dismutase chemistry, Trypanosoma cruzi enzymology
- 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) from Trypanosoma cruzi, Leishmania major and Babesia bovis. Comparison with existing structures from Plasmodium and other trypanosome isoforms shows a very conserved overall fold with subtle differences. In particular, structural data suggest that B. bovis FeSOD may display similar resistance to peroxynitrite-mediated inactivation via an intramolecular electron-transfer pathway as previously described in T. cruzi FeSOD isoform B, thus providing valuable information for structure-based drug design. Furthermore, lysine-acetylation results in T. cruzi indicate that acetylation occurs at a position close to that responsible for the regulation of acetylation-mediated activity in the human enzyme.
- Published
- 2015
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