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Overlay of X-ray cocrystal structures of Dot1L with 6 (ligand green, parts of the protein green) and 7 (ligand blue, protein gray).23 Amino acid side chains engaging in key interactions with the ligands are illustrated as sticks; polar contacts are highlighted as dotted red lines. Growth vectors (solid red arrow) open in ortho- and meta-positions for 6, but blocked for 7 due to tighter engagement of the flexible loop.
