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. 2016 Oct 14;59(21):9928–9941. doi: 10.1021/acs.jmedchem.6b01315

Figure 4.

Figure 4

Comparison of the EZH2 C-terminus with the SET domain active site. (A) Human PRC2 complex with compound 10. (PDB ID: 5LS6) (B) Equivalent region of the human PRC2-H3K27M-SAH complex, (PDB ID: 5HYN) with cofactor (orange) and histone H3 peptide (red). (C) Overlay of residues forming the SET domain lysine channel for both complexes, highlighting that the position of the C-terminus conformation observed in the compound complex is incompatible with substrate binding (red). (D) and (E) Surface representations showing that the lysine binding channel is closed in the PRC2-compound 10 complex (PDB ID: 5LS6) but accessible in the SAH/substrate complex (PDB ID: 5HYN). (F) Surface representation of EZH2 observed in the PRC2-compound 10 complex but with the H3 peptide overlaid from the PRC2-H3K27M-SAH complex, confirming that substrate binding is incompatible with the EZH2 conformation in the PRC2-compound 10 complex.