Structural Basis for the Inhibition of Histone Deacetylase 8 (HDAC8), a Key Epigenetic Player in the Blood Fluke Schistosoma mansoni
Figure 4
Ligand-triggered gating of the smHDAC8 active site pocket.
Close-up view of the active sites of the (A) smHDAC8/SAHA, (B) hHDAC8/SAHA (PDB 1T69), (C) smHDAC8/M344, and (D) hHDAC8/M344 (PDB 1T67) complexes shown as ribbon and sticks (upper panels), surface view (middle panels), and side cut-away surface view (lower panels). The conformational changes of smHDAC8 Y99 and F151 compared to hHDAC8 Y100 and F152 strongly influence the binding modes of the SAHA and M344 inhibitors to these enzymes.