Figure 4. KDAC8 requires a negatively charged 101 residue to deacetylate and interact with FRK^acRW.

(A) KDAC8 variants containing substitutions at the 101 position were reacted with FRK^acRW. Average specific activity was normalized such that the activity of wild-type KDAC8 with FRK^acRW was represented as 1. Error bars represent standard deviations (n≥4), and p-values are shown for statistically significant differences between activity of WT enzyme and variants. (B) Results of MD analysis identifying interactions between specific residues of KDAC8 and FRK^acRW reacted in panel A. 101x refers to the residue at position 101 in each KDAC variant. Shading corresponds to the percent of time a particular interaction was observed during MD simulations.