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Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
Published on: February 27, 2016
Structure of the histone deacetylase SIRT2
M S Finnin1, J R Donigian, N P Pavletich
1Cellular Biochemistry and Biophysics Program, and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature Structural Biology
|June 28, 2001
Summary
Human SIRT2, a Sir2 homolog, is crucial for life span regulation. Its crystal structure reveals an NAD-binding domain and a helical/zinc-binding module, identifying a potential catalytic site and a class-specific protein-binding pocket.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Sir2 proteins are NAD-dependent deacetylases regulating gene silencing and lifespan.
- Human SIRT2 is a homolog of yeast Sir2, involved in cellular processes.
- Understanding SIRT2 structure is key to its function.
Purpose of the Study:
- To determine the crystal structure of the human SIRT2 catalytic core.
- To identify potential catalytic and protein-binding sites within SIRT2.
Main Methods:
- X-ray crystallography of the 323 amino acid catalytic core of human SIRT2.
- Mutagenesis studies to probe catalytic activity.
Main Results:
- The 1.7 Å crystal structure revealed an NAD-binding domain (Rossmann fold variant) and a helical/zinc-binding module.
- A conserved groove at the domain interface is the likely catalytic site.
- A pocket within the helical module, lined with conserved hydrophobic residues, suggests a class-specific protein-binding site.
Conclusions:
- The structure provides insights into SIRT2's catalytic mechanism.
- A conserved pocket indicates potential for class-specific protein interactions.
- This structural information aids in understanding SIRT2's role in biological processes.
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