Figure 2.

(A) X-ray cocrystal structure of Dot1L (gray) with 2 (blue) (PDB code 5drt). Amino acid side chains engaged in key interactions with the ligand are illustrated as sticks. Key polar interactions of Dot1L and 2 are shown as red dotted red lines, the tetrahedral coordination of the two waters ligating Asp161 as gray dotted lines. (B) Comparison of the flexible loop (amino acids 126–140) in Dot1L bound to 2 (blue, protein gray) (PDB code 5drt) and SAM (green) (PDB code 3qow). (C) Overlay of ligands 2 (blue) (PDB code 5drt) and EPZ-5676 (green) (PDB code 4hra) bound to Dot1L in the same view as 2A. PyMol was used for structural visualization and figure preparation.²⁵