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Figure 5 Key differences between HDAC6 and HDAC8 in the coordination of the substrate. The active sites of HDAC6 (receptor from PDB ID 6WSJ, substrate from 5EFN for visualization purposes, orange) and HDAC8 (PDB ID 2V5W, teal) are overlaid. The loops that distinguish the two HDACs are highlighted (orange and teal), together with conformations generated for modeling substrate activity (grey). Residues S531 (HDAC6) and D101 (HDAC8) that coordinate hydrogen bonding (light blue: HDAC6, yellow: HDAC8) to the backbone of the acetylated substrate lysine residue, are also highlighted, as well as positions W459 (HDAC6) and Y100 (HDAC8). The hydroxamic acid inhibitors are shown in sticks, and the catalytic Zn2+ ions are shown as a white sphere. See Text for more details.