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. 2021 Aug 25;26(17):5151. doi: 10.3390/molecules26175151

Figure 11.

Figure 11

(A) Structural overlay of HDAC8 complexed with the α-amino amide 35 (PDB ID: 3FSH/green) and a hydroxamic acid (PDB ID: 1W22/red). Shown is the clipped binding pocket and the foot pocket with the zinc ion as a gray sphere and metal contacts as dotted orange lines. (B) Conformational changes leading to the enlargement of the foot pocket. W141 rotates away, enlarging the lower half, and Y306 and F152 rotate in a codependent manner enlarging the upper half of the foot pocket. (C) The 2D ligand interactions of in (A) overlaid crystal structures of a hydroxamic acid and 35 with PDB IDs 1W22 and 3SFH, respectively. (D) Binding mode of α-amino amides and indicated potency trends for bulky substituents. Metal bonds are shown as dotted orange lines.