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

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 in...

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Published in:Scientific reports 2016-09, Vol.6 (1), p.33133-33133, Article 33133
Main Authors: Tairum, Carlos A, Santos, Melina Cardoso, Breyer, Carlos A, Geyer, R Ryan, Nieves, Cecilia J, Portillo-Ledesma, Stephanie, Ferrer-Sueta, Gerardo, Toledo, Jr, José Carlos, Toyama, Marcos H, Augusto, Ohara, Netto, Luis E S, de Oliveira, Marcos A
Format: Article
Language:English
Subjects:
Cancer
Catalysis
Crystal structure
Cysteine
Host-pathogen interactions
Neurodegeneration
Peroxiredoxin
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Summary: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-π) 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-π 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep33133