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Updated: May 13, 2026
14:32
Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
Published on: February 27, 2016
Insight the C-site pocket conformational changes responsible for sirtuin 2 activity using molecular dynamics
Sugunadevi Sakkiah1, Mahreen Arooj, Guang Ping Cao
1Division of Applied Life Science (BK21 Program), Systems and Synthetic Agrobiotech Center (SSAC), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, South Korea.
Plos One
|March 26, 2013
Summary
Sirtuin 2 (SIRT2) deacetylation activity is regulated by conformational changes in its catalytic site, influenced by substrate/NAD(+) and inhibitors. Understanding these structural dynamics can enhance SIRT2 inhibitor development.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Sirtuins are NAD(+)-dependent deacetylases regulating critical cellular processes.
- SIRT2 mutations (Q167A, H187A) reduce activity, but structural basis remains unclear.
Purpose of the Study:
- To investigate the structural dynamics of wild-type (WT) and mutant SIRT2.
- To elucidate the role of substrate/NAD(+) and inhibitors in SIRT2 structural changes.
Main Methods:
- 5 ns molecular dynamics (MD) simulations of SIRT2 Apo-form.
- MD simulations of WT, Q167A, and H187A SIRT2 complexes with substrate/NAD(+) and inhibitor.
Main Results:
- Substrate/NAD(+) binding induces C-site assembly, while inhibitor binding causes disassembly.
- Interactions involving F96 and the F96-H187 distance are key to C-site dynamics.
- Conformational changes in the L3 loop significantly impact C-site assembly/disassembly.
Conclusions:
- Distinct L3 loop conformational changes and C-site dynamics are crucial for SIRT2 deacetylation.
- Elucidating SIRT2 structural changes aids in improving the potency of SIRT2 inhibitors.
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