Investigation of structural transitions and reactivity over hydroperoxides of Tsa1p (Thiol Specific Antioxidant Protein 1) from Saccharomyces cerevisiae.

Author(s)

Carlos Abrunhosa Tairum Junior

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2015-07-03

Examining board members

Marcos Antonio de Oliveira; José Ribamar dos Santos Ferreira Júnior; Flavia Carla Meotti; Luis Eduardo Soares Netto; Gisele Monteiro de Souza

• Advisor: Marcos Antonio de Oliveira

Abstract

2-Cys Prx constitute a group of homodimeric antioxidant enzymes that act in the decomposition of hydroperoxides using a reactive cysteine (peroxidase cysteine - CysP). The high reactivity of the CysP is achieved by the participation of two vicinal amino acids: a threonine and an arginine, which constitute the catalytic triad. After the decomposition of hydroperoxide, the CysP forms an intermolecular disulfide with a second cysteine residue (resolving cysteine - CysR), which is reduced by the thioredoxin (Trx). During the redox cycle, these enzymes undergo to changes in the structure, but the molecular mechanisms involved in this process were poorly understood. In this study we have obtained the crystallographic structure of the 2-Cys Prx enzyme Tsa1 from Saccharomyces cerevisiae. By means of biochemical and molecular biology approaches, the importance of amino acids involved in reactivity and structural transitions were determined. Finally, efforts have been performed to the determination of the crystallographic structures of mutant proteins obtained in this study. (AU)

• FAPESP's process: 10/00172-8 - Investigation of structural transitions and reactivity towards TSA1 (thiol specific antioxidant protein 1) peroxides of Saccharomyces cerevisiae
• Grantee: Carlos Abrunhosa Tairum Junior
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)