Fig 9. The mechanism of action of HDAC4.

As compared to HDAC class I, HDAC class IIa enzymes exhibit significantly reduced ability to deacetylate. In class IIa enzymes the His976 located in the same position in the catalytic site as Tyr306 in class I HDACs does not serve as a hydrogen bond donor to bind to the carbonyl oxygen of the leaving acetyl group and thus reduces the susceptibility of carbonyl carbon to nucleophilic attack by the water, as in HDAC class I (see Fig 4).