Figure 2. The −1 substrate position participates in an ionic interaction with KDAC8.

(A) Peptides derived from FRK^acRW, where residues were substituted with alanine, were reacted with KDAC8. Average specific activity was normalized such that the activity of 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 with FRK^acRW and activity with each other substrate. (B) Results of MD analysis identifying interactions between specific residues of KDAC8 and the derivative peptide substrates reacted in panel A. x(+1) refers to the substrate residue in the +1 position for each peptide. Shading corresponds to the percent of time a particular interaction was observed during MD simulations.