title: Iron superoxide dismutases in eukaryotic pathogens: new insights from Apicomplexa and Trypanosoma structures.
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.
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
authors.forename: Isabelle Q H
authors.initials: IQ
authors.lastname: Phan
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Davies
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors.forename: Nilmar Silvio
authors.initials: NS
authors.lastname: Moretti
authors.affiliation: CSIR-National Chemical Laboratory, Pune 411 008, India.
authors.forename: Dhanasekaran
authors.initials: D
authors.lastname: Shanmugam
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Cestari
authors.affiliation: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors.forename: Atashi
authors.initials: A
authors.lastname: Anupama
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Fairman
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Edwards
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Stuart
authors.affiliation: Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Schenkman
authors.affiliation: Seattle Structural Genomics Center for Infectious Disease (SSGCID), USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Myler
mesh_terms: D000595:Amino Acid Sequence; D016782:Apicomplexa / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D016793:Babesia bovis / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D056890:Eukaryota / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D018320:Leishmania major / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics
chemical_list: D013482:Superoxide Dismutase
keywords: Apicomplexa; Trypanosoma; iron superoxide dismutase