Figure 7.

C153F HDAC8. (a) Superimposition of the HDAC8 C153F‐SAHA complex (C = yellow, N = blue, O = red, S = green, Zn²⁺ = yellow sphere, SAHA = tan) and the wild‐type HDAC8‐SAHA complex (PDB 1T69) (C = blue, Zn²⁺ = blue sphere, SAHA = gray). Water molecules (red spheres) occupy the space previously occupied by the C153 side chain. The F153 side chain sterically locks W141 in the “in” conformation. (b) The solvent‐accessible surface of wild‐type HDAC8 shows that the W141 side chain, which is in equilibrium between the “in” and “out” conformations, serves as a gate for acetate release channels. When W141 is in the “out” conformation, the channels are open. (c) Corresponding view of C153F HDAC8 shows that when W141 is locked in the “in” conformation by the F153 side chain, the acetate release channels are completely blocked. Reprinted with permission from ref. 26. Copyright 2014, American Chemical Society.