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Updated: Jun 4, 2026
14:32
Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
Published on: February 27, 2016
Structure and biochemical functions of SIRT6
Patricia W Pan1, Jessica L Feldman, Mark K Devries
1Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
The Journal of Biological Chemistry
|March 3, 2011
Summary
SIRT6 exhibits low histone deacetylase activity and unique structural features, suggesting it may function as an NAD(+) metabolite sensor rather than a typical sirtuin enzyme.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- SIRT6 is an NAD(+)-dependent deacetylase involved in genomic stability and glucose metabolism.
- Its precise molecular functions, including ADP-ribosylation versus histone deacetylation, remain debated.
- Understanding SIRT6's enzymatic activity is crucial for elucidating its biological roles.
Purpose of the Study:
- To investigate the mechanistic basis of SIRT6's enzymatic activity.
- To elucidate the structural features contributing to SIRT6's function.
- To determine SIRT6's interaction with NAD(+) and its substrates.
Main Methods:
- Biochemical and kinetic assays to measure deacetylation rates.
- X-ray crystallography to determine SIRT6 structures.
- Isothermal titration calorimetry and fluorescence binding assays to study NAD(+) and ADP-ribose interactions.
Main Results:
- SIRT6 exhibits histone deacetylation activity approximately 1,000 times slower than other sirtuins.
- Unique structural elements in SIRT6 include a splayed zinc-binding domain and altered NAD(+)-binding loop.
- SIRT6 binds NAD(+) with high affinity independently of acetylated substrates, unlike other sirtuins.
Conclusions:
- SIRT6 possesses distinct structural and biochemical properties compared to other sirtuins.
- These unique features suggest a novel activation mechanism or a role as an NAD(+) metabolite sensor.
- Further research is needed to fully define SIRT6's function in cellular processes.
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