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. Author manuscript; available in PMC: 2018 Feb 20.
Published in final edited form as: Chem Rev. 2017 Mar 24;118(3):989–1068. doi: 10.1021/acs.chemrev.6b00801

Figure 21.

Figure 21

(A) Cofactor binding site of DOT1L (PDB ID: 1NW3). (B) Crystal structure of DOT1L in complex with EPZ004777 (PDB ID: 4ER3). Conformational rearrangements of DOT1L create a cavity to accommodate the t-butylphenyl group. (C) Overlay of DOT1L-SAM and DOT1L-EPZ004777 showing conformational rearrangement of substrate-binding and activation loop residues (magenta and yellow, respectively). (D) Overlay of DOT1L-EPZ004777 (PDB ID: 4ER3) and DOT1L-EPZ-5676 (PDB ID: 4HRA) complexes. Key hydrogen bonds are represented as green dashed lines between EPZ004777 (blue) and DOT1L and EPZ-5676 is depicted in orange.