title: Catalytic Thr or Ser Residue Modulates Structural Switches in 2-Cys Peroxiredoxin by Distinct Mechanisms.
abstract: 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.
authors.affiliation: Instituto de Biociências, Campus do Litoral Paulista, Universidade Estadual Paulista Júlio de Mesquita Filho, São Vicente, São Paulo, 11330-900, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Tairum
authors.affiliation: Instituto de Biociências, Campus do Litoral Paulista, Universidade Estadual Paulista Júlio de Mesquita Filho, São Vicente, São Paulo, 11330-900, Brazil.
authors.forename: Melina Cardoso
authors.initials: MC
authors.lastname: Santos
authors.affiliation: Instituto de Biociências, Campus do Litoral Paulista, Universidade Estadual Paulista Júlio de Mesquita Filho, São Vicente, São Paulo, 11330-900, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Breyer
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, 05508-090, Brazil.
authors.forename: R Ryan
authors.initials: RR
authors.lastname: Geyer
authors.affiliation: Facultad de Ciencias - Universidad de la República - Montevideo, Uruguay.
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Nieves
authors.affiliation: Facultad de Ciencias - Universidad de la República - Montevideo, Uruguay.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Portillo-Ledesma
authors.affiliation: Facultad de Ciencias - Universidad de la República - Montevideo, Uruguay.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferrer-Sueta
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto - SP, 14040-901, Brazil.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Toledo
authors.affiliation: Instituto de Biociências, Campus do Litoral Paulista, Universidade Estadual Paulista Júlio de Mesquita Filho, São Vicente, São Paulo, 11330-900, Brazil.
authors.forename: Marcos H
authors.initials: MH
authors.lastname: Toyama
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, 05508-090, Brazil.
authors.forename: Ohara
authors.initials: O
authors.lastname: Augusto
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, 05508-090, Brazil.
authors.forename: Luis E S
authors.initials: LE
authors.lastname: Netto
authors.affiliation: Instituto de Biociências, Campus do Litoral Paulista, Universidade Estadual Paulista Júlio de Mesquita Filho, São Vicente, São Paulo, 11330-900, Brazil.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: de Oliveira