User:Asif Hossain/Sandbox 1: Difference between revisions

The pentacoordinated Zn²⁺ ion involved in the metalloenzyme catalysis is tethered to the protein through interactions with <scene name='81/811085/Zinc_binding/2'>Asp178, His180, and Asp267</scene>. This positions the metal ion to favorably interact with the catalytic water and acetylated lysine substrate. <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 Zn²⁺ ion lowers the pKa of a water molecule that activates it as a nucleophile. By binding to both the nucleophile and the substrate simultaneously, the Zn²⁺ ion also assists the deacetylation process by lowering the entropy of the reaction. Thus, the the Zn²⁺ polarizes the carbonyl of the acetyl-lysine and stabilizes the transition state.<ref name="Somoza">Somoza J, Skene R. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure, 12(7), 1325-1334.2004. https://doi.org/10.1016/j.str.2004.04.012 </ref>