Iron superoxide dismutases in eukaryotic pathogens: new insights from Apicomplexa and Trypanosoma structures. Issue 5 (1st May 2015)

• Record Type: Journal Article
• Authors: Phan, Isabelle Q. H.; Davies, Douglas R.; Moretti, Nilmar Silvio; Shanmugam, Dhanasekaran; Cestari, Igor; Anupama, Atashi; Fairman, James W.; Edwards, Thomas E.; Stuart, Kenneth; Schenkman, Sergio; Myler, Peter J.
• Is Part Of: Acta crystallographica. Volume 71:Issue 5(2015:May)
• Page Start: 615
• Page End: 621
• Publication Date: 2015-05-01
• Subjects: Crystallography -- Periodicals; Crystals -- Periodicals; 548
• DOI: 10.1107/S2053230X15004185
• Languages: English
• ISSNs: 2053-230X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>Trypanosoma cruzi</italic>, <italic>Leishmania major</italic> and <italic>Babesia bovis</italic>. Comparison with existing structures from <italic>Plasmodium</italic> and other trypanosome isoforms shows a very conserved overall fold with subtle differences. In particular, structural data suggest that <italic>B. bovis</italic> FeSOD may display similar resistance to peroxynitrite‐mediated inactivation <italic>via</italic> an intramolecular electron‐transfer pathway as previously described in <italic>T. cruzi</italic> FeSOD isoform B, thus providing valuable information for structure‐based drug design. Furthermore, lysine‐acetylation results in <italic>T. cruzi</italic> indicate that acetylation occurs at a position close to that responsible for the regulation of acetylation‐mediated activity in the human enzyme.</p> </abstract>