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Updated: Jul 27, 2025
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Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
Published on: February 27, 2016
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Nicotinamide riboside activates SIRT5 deacetylation
Alyson M Curry1, Stacia Rymarchyk2, Noah B Herrington1
1Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
The FEBS Journal
|June 8, 2023
Summary
Researchers discovered nicotinamide riboside (NR) as the first SIRT5-selective activator. This finding enhances understanding of SIRT5
Area of Science:
- Biochemistry and Molecular Biology
- Cellular Metabolism and Aging
Background:
- Human sirtuins (enzymes regulating cellular events) are linked to longevity and age-related diseases.
- SIRT5, a mitochondrial sirtuin, is crucial for cardiac and neuronal health but its deacetylase function is debated.
- Targeting sirtuin activity with small molecules is a therapeutic strategy for age-related disorders.
Purpose of the Study:
- To investigate the catalytic activity and regulation of the mitochondrial sirtuin SIRT5.
- To identify specific activators of SIRT5 to probe its biological functions.
- To explore the therapeutic potential of modulating SIRT5 activity.
Main Methods:
- Identification of a SIRT5-selective allosteric activator, nicotinamide riboside (NR).
- Biochemical assays to assess NR's effect on SIRT5 catalytic efficiency with peptide substrates.
- Molecular biology and structural biology approaches to map the NR binding site and explore the mechanism of action.
Main Results:
- Nicotinamide riboside (NR) was identified as the first small molecule to selectively activate SIRT5.
- NR significantly increases SIRT5's catalytic efficiency.
- The binding site for NR on SIRT5 was mapped, providing structural insights.
Conclusions:
- Nicotinamide riboside (NR) serves as a valuable chemical probe for studying SIRT5's cellular roles.
- The discovery guides the development of more potent and selective SIRT5 activators.
- Targeted SIRT5 activation holds promise for treating metabolic and age-related diseases.
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