Deciphering the Allosteric Activation Mechanism of SIRT6 Using Molecular Dynamics Simulations.

ABSTRACT: As a member of the histone deacetylase protein family, the NAD⁺-dependent SIRT6 plays an important role in maintaining genomic stability and regulating cell metabolism. Interestingly, SIRT6 has been found to have a preference for hydrolyzing long-chain fatty acyls relative to deacetylation, and it can be activated by fatty acids. However, the mechanisms by which SIRT6 recognizes different substrates and can be activated by small molecular activators are still not well understood. In this study, we carried out extensive molecular dynamic simulations to shed light on these mechanisms. Our results revealed that the binding of the myristoylated substrate stabilizes the catalytically favorable conformation of NAD⁺, while the binding of the acetyl-lysine substrate leads to

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC10530556 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature