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Updated: Jun 26, 2026
14:55
Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Crystal structure of a SIR2 homolog-NAD complex
J Min1, J Landry, R Sternglanz
1W. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cell
|May 5, 2001
Summary
The SIR2 protein family, crucial for DNA repair and lifespan extension, are nicotinamide-adenine dinucleotide (NAD)-dependent deacetylases. Structural analysis reveals their unique NAD binding and catalytic mechanisms.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- The SIR2 protein family are nicotinamide-adenine dinucleotide (NAD)-dependent protein deacetylases.
- These enzymes are involved in critical cellular processes including transcriptional silencing, DNA repair, and lifespan extension in yeast.
Purpose of the Study:
- To elucidate the structural basis of NAD binding and catalytic mechanism of SIR2 homologs.
- To provide insights into the function of this important enzyme family.
Main Methods:
- X-ray crystallography was used to determine the structures of a SIR2 homolog from Archaeoglobus fulgidus.
- Two crystal structures were solved at 2.1 A and 2.4 A resolutions, with the enzyme complexed to NAD.
Main Results:
- The determined structures reveal a two-domain protein architecture: a large domain with a Rossmann fold and a small domain with a zinc ribbon motif.
- Nicotinamide-adenine dinucleotide (NAD) is bound in a pocket situated between these two domains.
- A distinct NAD binding mode and an unusual zinc ribbon configuration were observed, offering insights into the enzyme's catalytic mechanism.
Conclusions:
- The structural insights provide a foundation for understanding the catalytic mechanism of NAD-dependent protein deacetylation by the SIR2 family.
- This research contributes to the broader understanding of gene regulation, DNA repair, and aging processes.
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