Figure 3: KDM4A can demethylate methylated lysine and arginine containing non-histone sequences.
From: Highly selective inhibition of histone demethylases by de novo macrocyclic peptides
(a) Overlay of views from crystal structures of KDM4A with CP2 (red) and CP2(R6Kme3).NOG (cyan). It is noteworthy that the binding site of NOG, an inactive 2OG analogue, is distinct from the binding site of CPs. (b) CP2(R6Kme3) (peptide 9) and (c) CP2(R6me2a) (peptide 10) are substrates of KDM4A. KDM4A1-359 (2 μM) was incubated with CP2 variant (10 μM) in the presence of 2OG (100 μM), Fe(II) (10 μM) and ascorbate (100 μM) for 2 h at 37 °C. The reaction product was analysed using matrix-assisted laser desorption/ionization–time of flight MS. Reactions containing enzymes are in red, no enzyme peptide controls are in black.
