Tier 3 — preclinical

Mechanistic basis of N-terminal domain-mediated allostery in SIRT6: integrating molecular dynamics simulations and biochemical assays

Haiyue Tang, Wenjie Ma, Guoyou Zhang, Jiacheng Wei, Jianyang Ao, Shaoyong Lu
Molecular Diversity 2026 30(3):3845-3856

Bibliography

PubMed
PMID 40885886
DOI
10.1007/s11030-025-11340-1

Study snapshot

DesignMolecular-dynamics simulation plus biochemical enzyme assays.
ModelWild-type and N-terminal-truncated SIRT6.
SampleBiochemical and simulation experiments.
InterventionN-terminal-domain truncation and structural/catalytic analysis.
DurationAcute biochemical assays and molecular simulations.
EndpointsNAD+ pocket conformation; NAD+ binding affinity; Substrate coordination; Catalytic geometry; Deacetylation efficiency

What the study showed, in plain terms

The SIRT6 N-terminal domain helps keep the NAD+ pocket and substrate in the geometry needed for efficient catalysis. Removing the N-terminal domain opened the NAD+ pocket and reduced deacetylation efficiency by about twofold.

Key findings

The N-terminal domain acts as part of an allosteric network linking NAD+ binding to substrate positioning, providing another structural site that may be exploitable for future SIRT6 modulators.

What this study can and cannot tell us

Mechanistic enzyme study only; no cellular, animal or human efficacy outcome and no direct test of fucoidan or a marketed supplement.

Citation network

Articles citing this research paper

1 article

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability