Histone deaceylases (HDACs) mediate regulation of gene expression via changes in nucleosome conformation. Deregulation of HDACs is associated with several cancers; while some inhibitors of HDACs have been shown to have antitumor effects, including induction of terminal differentiation and prevention of tumor formation in animal models.
An HDAC-homologue from Aquifex aeolicus shares histone deacetylase activity with mammalian HDACs and is also inhibited by HDAC inhibitors. The structure of this protein revealed it to be a Zn-dependent metallozenzyme with the active site at the base of a deep pocket.
HDAC inhibitors act by blocking this pocket and also by coordinating the zinc at the base of the active site.
