Epigenetic alterations play
important roles in a wide variety of physiological and pathological events. As
one of the most important epigenetic regulators, Histone Deacetylases (HDACs)
are able to deacetylate lysine residues on histone and non-histone proteins,regulating chromatin structure, gene expression and protein function. Eighteen
human HDACs have been identified and grouped into 4 classes based on their
homology to respective yeast orthologous. The human sirtuins family, homologs of
the yeast silent information regulator 2(Sir2), belongs to class III HDACs.
They are NAD+-dependent deacetylases and contain seven members (SIRT1-7) with
varied functions, structures, and localizations. Among them, SIRT1 is the most
extensively studied, primarily because of its regulation of diverse cellular
targets and functions as well as its therapeutic potential.
Human SIRT1 comprises 747 amino
acids divided into three main regions: the central core, possessing the
deacetylase domain, which consists of a large NAD+-binding subdomain with a
Rossmann fold and a smaller subdomain composed of a helical module and a Zn2+-
binding module, and the N- and C-terminal domains, containing regulatory
elements and binding domains for SIRT1 co-activators or repressors.(Read more)

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