Homology model of the active site of EZH2. The model is based on sequence and structure alignment with histone dimethyltransferase G9a/EHMT2 (PDBID 2O8J).⁹  This was also structurally aligned with GLP/EHMT1 bound to an H3K9me2 peptide substrate (PDBID 2RFI), and SETD7 (PDBID 1O9S) using ICM software, Version 3.6-1g (Molsoft LLC).¹⁷  See supplemental Figures 6-8 for sequence and structural alignments. The model shows the reaction products dimethyllysine and S-adenosylhomocysteine (SAH) in purple. The black arrow indicates the path of methyl transfer from the sulfur atom (yellow) of the cofactor to the nitrogen atom (blue) of substrate lysine. Hydrogen bonds are shown as dotted blue lines.