Zinc-dependent histone deacetylase (HDAC) (HDAC)

Zinc-dependent histone deacetylases (HDACs) are essential enzymes that regulate gene expression by removing acetyl groups from lysine residues on histone tails and various non-histone proteins (UniProt, 2023). This enzymatic activity is mediated by a catalytic zinc ion (Zn2+) coordinated within a deep hydrophobic pocket, which facilitates the hydrolysis of the amide bond in acetylated lysines (Seto & Yoshida, 2014). By promoting chromatin condensation, HDACs typically act as transcriptional repressors and are vital for maintaining cellular homeostasis, including cell cycle progression and apoptosis (Ho et al., 2020). In many cancers, HDACs are overexpressed or dysregulated, leading to the silencing of tumor suppressor genes and promoting oncogenesis (Falkenberg & Johnstone, 2014). Therapeutic intervention focuses on small-molecule inhibitors that contain a zinc-binding group, such as a hydroxamate or benzamide, which chelates the active-site zinc to block substrate access and restore normal acetylation levels (PubMed, 2020).

Other names

Histone deacetylaseLysine deacetylaseKDACZinc-dependent HDAC active siteHDAC zinc coordination pocket

Inhibition of enzymatic activity through chelation of the catalytic zinc ion within the active site, preventing the deacetylation of lysine residues on histones and non-histone proteins.