Iron superoxide dismutases in eukaryotic pathogens: new insights from Apicomplexa and Trypanosoma structures

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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.

• Tipo de documento: Artigo Científico
• Fonte: ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS; v. 71, p. 7-pg., 2015-05-01.

Resumo

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. (AU)

• Processo FAPESP: 13/20074-9 - Estudo dos níveis de acetilação protéica em Trypanosoma cruzi
• Beneficiário: Nilmar Silvio Moretti
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 12/09403-8 - Estudo do papel das modificações de cromatina nos mecanismos de reparo de dano no DNA e controle da transcrição em Trypanosoma
• Beneficiário: Nilmar Silvio Moretti
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/51973-3 - Mecanismo de sinalização celular de Trypanosoma em resposta a alterações nutricionais e agentes genotóxicos
• Beneficiário: Sergio Schenkman
• Modalidade de apoio: Auxílio à Pesquisa - Temático