Structure of the MLL1-SET domain bound to the H3 peptide and cofactor product S-adenosyl-L-homocysteine (AdoHcy) (pdb code 2W5Y). Note that an MLL3 structure currently is not available. (A) The protein is shown as blue ribbon, and the peptide is shown in orange in the stick model with the target nitrogen atom colored white. The residues corresponding to Asn4848 and Tyr4884 are displayed in red and green, respectively, the corresponding alignment of MLL1 and MLL3 is shown in Additional file 1: Figure S4. (B) Details of the MLL1-SET structure showing that N3906 (corresponding to N4848) is involved in an H-bond to AdoMet (shown in stick model with coloring by atom type). (C) Details of the MLL1-SET structures showing the hydrophobic and aromatic pocket of MLL1 surrounding the target nitrogen atom which consists of Y3942 (corresponding to Y4884, shown in green) and Y4800, I4847, and Y4885 (all designations refer to MLL3, residues shown in blue).