deacetylase

Deacetylase refers to an enzyme that catalyzes the removal of acetyl groups from acetylated substrates, most commonly lysine residues on histone and non-histone proteins. By reversing acetylation, deacetylases regulate charge, conformation, and interactions of target proteins, influencing chromatin structure, gene expression, metabolism, and signaling pathways.

Two major families operate in eukaryotes. Zinc-dependent histone deacetylases (HDACs) use a Zn2+ ion in their catalytic site to hydrolyze the acetyl group and are categorized into classes I, II, and IV based on sequence similarity and localization. The NAD+-dependent sirtuins (class III) remove acetyl groups through a mechanism that consumes NAD+ and yields nicotinamide and O-acetyl-ADP-ribose. Bacteria and some archaea also possess deacetylases with distinct cofactors and substrate preferences.

Most studied substrates are histones, where deacetylation promotes chromatin condensation and transcriptional repression, but numerous non-histone proteins—including transcription factors, enzymes, and cytoskeletal components—are regulated by acetylation and deacetylation.

Physiological roles span development, differentiation, DNA repair, metabolism, and aging. Dysregulation of deacetylase activity is associated with cancer, neurodegenerative diseases, and metabolic disorders. Therapeutic interest includes inhibitors targeting zinc-dependent HDACs and modulators of sirtuin activity, explored for cancer treatment and age-related diseases.