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Methods to Identify the NMR Resonances of the 13C-Dimethyl N-terminal Amine on Reductively Methylated Proteins
Published on: December 12, 2013
Identification of activators of methionine sulfoxide reductases A and B
Predrag Cudic1, Neelambari Joshi2, Daphna Sagher2
1Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida, USA.
Abstract:
The methionine sulfoxide reductase (Msr) family of enzymes has been shown to protect cells against oxidative damage. The two major Msr enzymes, MsrA and MsrB, can repair oxidative damage to proteins due to reactive oxygen species, by reducing the methionine sulfoxide in proteins back to methionine. A role of MsrA in animal aging was first demonstrated in Drosophila melanogaster where transgenic flies over-expressing recombinant bovine MsrA had a markedly extended life span. Subsequently, MsrA was also shown to be involved in the life span extension in Caenorhabditis elegans. These results supported other studies that indicated up-regulation, or activation, of the normal cellular protective mechanisms that cells use to defend against oxidative damage could be an approach to treat age related diseases and slow the aging process. In this study we have identified, for the first time, compounds structurally related to the natural products fusaricidins that markedly activate recombinant bovine and human MsrA and human MsrB.
Insights
New compounds activate methionine sulfoxide reductase (Msr) enzymes, which protect cells from oxidative damage. This discovery offers a potential strategy for slowing aging and treating age-related diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Gerontology
Background:
- Methionine sulfoxide reductase (Msr) enzymes, MsrA and MsrB, repair oxidative damage to proteins.
- MsrA has been linked to lifespan extension in model organisms like Drosophila melanogaster and Caenorhabditis elegans.
- Activating cellular protective mechanisms against oxidative stress is a potential therapeutic approach for age-related diseases.
Purpose of the Study:
- To identify novel compounds that activate Msr enzymes.
- To investigate the potential of these compounds in modulating cellular oxidative damage repair pathways.
Main Methods:
- Screening of compounds structurally related to natural product fusaricidins.
- Assaying the activation of recombinant bovine and human MsrA and human MsrB enzymes.
Main Results:
- Identification of novel compounds that significantly activate both MsrA and MsrB.
- Demonstration of marked activation of recombinant bovine and human MsrA and human MsrB by these compounds.
Conclusions:
- Compounds structurally related to fusaricidins can activate Msr enzymes.
- These activators represent a new class of molecules with potential therapeutic applications in aging and oxidative stress-related diseases.
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