Fig. 1

Structural details of the N-terminal region of KDM4A (JMJD2A). A Crystal structure of KDM4A (JMJD2A) in complex with 2-OG (PDB 5TVR), which shows a close interaction between the JmjC domain and the JmjN domain, in red and light blue, respectively. B Crystal structure of JMJD2A complexed with histone H3 peptide trimethylated at Lys9 (PDB code: 2OQ6). 2-OG is shown in green sticks, H3 peptide in light blue sticks, and Nickel ion in green sphere. The histone substrate is bound in a broad hydrophobic cleft by adopting a bent conformation with the methylated nitrogen of the lysine side chain oriented towards the metal ion, in order to enable the catalytic reaction. C and D Detailed view of 2-OG binding mode in 2D and 3D, respectively. The hydrogen bonds are depicted in yellow and electrostatic interactions in magenta. 2-OG interacts through a salt bridge with Lys 206, and H-bonds with both Lys206 and Tyr132