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. Author manuscript; available in PMC: 2015 Nov 2.
Published in final edited form as: Biochemistry. 2015 Oct 14;54(42):6501–6513. doi: 10.1021/acs.biochem.5b00881

Figure 2.

Figure 2

Summary of the HDAC8 mechanism. Coordination to Zn2+ and hydrogen bonding with Y306 activates the scissile carbonyl of acetyllysine for nucleophilic attack by a Zn2+-bound water molecule with the assistance of general base H143. Electrostatic stabilization of the resulting tetrahedral intermediate is achieved by Zn2+ and H142. Proton donation to the leaving amino group by H143 enables collapse of the tetrahedral intermediate to form free lysine and acetate.