Catalytic Thr or Ser Residue Modulates Structural Switches in 2-Cys Peroxiredoxin by Distinct Mechanisms

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Tairum, Carlos A. ; Santos, Melina Cardoso ; Breyer, Carlos A. ; Ryan Geyer, R. ; Nieves, Cecilia J. ; Portillo-Ledesma, Stephanie ; Ferrer-Sueta, Gerardo ; Toledo, Jr., Jose Carlos ; Toyama, Marcos H. ; Augusto, Ohara ; Netto, Luis E. S. ; de Oliveira, Marcos A.

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 6, SEP 15 2016.
• Citações Web of Science: 11

Resumo

Typical 2-Cys Peroxiredoxins (2-Cys Prxs) reduce hydroperoxides with extraordinary rates due to an active site composed of a catalytic triad, containing a peroxidatic cysteine (CP), an Arg, and a Thr (or Ser). 2-Cys Prx are involved in processes such as cancer; neurodegeneration and host-pathogen interactions. During catalysis, 2-Cys Prxs switch between decamers and dimers. Analysis of 2-Cys Prx structures in the fully folded (but not locally unfolded) form revealed a highly conserved, non-conventional hydrogen bond (CH-p) between the catalytic triad Thr of a dimer with an aromatic residue of an adjacent dimer. In contrast, structures of 2-Cys Prxs with a Ser in place of the Thr do not display this CH-p bond. Chromatographic and structural data indicate that the Thr (but not Ser) destabilizes the decamer structure in the oxidized state probably through steric hindrance. As a general trend, mutations in a yeast 2-Cys Prx (Tsa1) favoring the dimeric state also displayed a decreased catalytic activity. Remarkably, yeast naturally contains Thr-Ser variants (Tsa1 and Tsa2, respectively) with distinct oligomeric stabilities in their disulfide states. (AU)

• Processo FAPESP: 07/50930-3 - Análise funcional e estrutural de proteínas antioxidantes dependentes de tióis: uma investigação de mecanismos moleculares de catálise e da formação de complexos protéicos contendo dissulfetos mistos
• Beneficiário: Marcos Antonio de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs