Histone deacetylase 8 (HDAC8): Difference between revisions

There are four major classes of [https://proteopedia.org/wiki/index.php/Histone_deacetylase HDAC] proteins (I,II, III, and IV). Other than the Class III “[https://en.wikipedia.org/wiki/Sirtuin sirtuins]” that utilize a NAD⁺ cofactor-dependent mechanism <ref name="Sauve">PMID:23102634</ref>, all other HDAC classes use Zn²⁺-assisted catalysis to activate a water molecule for nucleophilic attack (Figure 2).<ref name="DesJarlais, R., & Tummino, P. J.">DesJarlais, R., & Tummino, P. J. (2016). Role of histone-modifying enzymes and their complexes in regulation of chromatin biology. Biochemistry, 55(11), 1584-1599. https://doi.org/10.1021/acs.biochem.5b01210 </ref> While Classes I, II, and IV do have some major distinctions such as size of the protein, in general, they share homology at the catalytic site. HDAC8 is classified as a Class I HDAC alongside HDACs 1-3. In fact, within Class I HDACs,  there are many invariant residues involved in the catalytic site (such as His-Asp dyads), Zn-binding, and ligand binding pocket (such as Asp101) (Figure 1). <ref name="Vannini, A., Volpari, C., Gallinari, P.">Vannini, A., Volpari, C., Gallinari, P., Jones, P., Mattu, M., Carfí, A., ... & Di Marco, S. (2007). Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8–substrate complex. EMBO reports, 8(9), 879-884. https://doi.org/10.1038/sj.embor.7401047 </ref> The structure reported here is of Human HDAC8, a 377 residue, Class I HDAC.