English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Tairum Junior CA. Investigation of Structural Transitions and Reactivity over Hydroperoxides of Tsa1p (Thiol Specific Antioxidant Protein 1) from Saccharomyces cerevisiae [Ph. D. thesis (Biotechnology)]. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo; 2015. Peroxiredoxins (Prx) of 2-Cys typical type are a subfamily of homodimeric antioxidants enzymes that can act on the decomposition of hydroperoxides, as molecular chaperones and in signal transduction. These enzymes decompose hydroperoxides using a highly reactive cysteine residue (peroxidatic cysteine CysP). Additionally, Prx contain two highly conserved amino acids near CysP represented by a threonine (or serine) and arginine which together are called catalytic triad. Besides the CysP, these enzymes possess a second cysteine residue (resolving cysteine CysR) which forms an intermolecular disulfide with CysP during the redox cycle that is often reduced by the enzyme thioredoxin (Trx). As mentioned above, Typical 2-Cys Prx present homodimer as minimal unit, but may be in the decameric form, by the formation of a pentamer of dimers and, under high concentrations of hydroperoxides, CysP of eukaryotic enzymes are overoxidized, leading to the formation of high molecular weight complexes with chaperone activity and involved in signal transduction. This study aimed to determine the roles of the catalytic triad residues and of the residues related to the structure and function of the Saccharomyces cerevisiae Tsa1 by site directed mutagenesis, besides making efforts to obtain the crystallographic structure of these mutants in order to achieve a better understanding of the interference caused by mutations in the structure. Initially the structure of the Tsa1 C47S was determined and from it was possible to conduct several structural analyzes and assess which amino acid residues would be relevant for further investigations. The results analysis revealed that Tsa1 E50A and Tsa1 R146Q mutants do not present Trx-dependent peroxidase activity, indicating that Glu 50 and Arg 146 residues are critical to Trx-Prx interaction, which represented one of the first structural approaches to the understanding of molecular aspects of the Prx reduction by Trx. Also, it was investigated the importance of the Asp 141 residue, which is conserved among Typical 2-Cys Prx, and showed significantly to affect the reduction process by Trx and DTT. The role of the catalytic triad amino acids was evaluated by using the mutants Tsa1 T44A , Tsa1 T44S , Tsa1 T44V , Tsa1 R123K and Tsa1 R123G . It was shown that Arg 123 is essential for reactivity while Thr 44 performs a CH- type interaction with a tyrosine in the adjacent dimer. It was observed that the presence of this interaction is necessary for the Tsa1 remains in decamer, which was related to the maximum peroxidase activity of the enzyme, while the dimeric enzyme showed great loss of activity, indicating an evident relationship between structure and function. Additionally, we demonstrated that all mutant enzymes generated in this study which had reduced activity also showed a lower susceptibility to CysP overoxidation. Thus, it is possible to conclude that there is a direct relationship between oligomeric state and reactivity of Tsa1, which also influences other processes related to this enzyme.

Investigação de transições estruturais e da reatividade sobre peróxidos de Tsa1p (Thiol Specific Antioxidant Protein 1) de Saccharomyces cerevisiae.