Fig. 1. Outline of N-demethylation catalysed by KDM6B. (a) Reaction scheme of KDM6B catalysis. Oxidation of an N-methyl C–H bond by KDM6B results in formation of an unstable hemiaminal, which fragments to form formaldehyde. (b) View from a crystal structure of KDM6B in complex with histone substrate (PDB ID: ; 4EZH).12 The methylated lysine-27 residue (red) protrudes towards the catalytic iron(ii) bound in the active site (for crystallographic purposes, nickel was substituted for iron). N-Oxalylglycine (green) is a structural analogue of 2-oxoglutarate. (c) Structures of lysine analogues used in this study. Note: the Lys(Me2), Lys(Me/Et), Lys(Et2), Lys(iPr) and Lys (Me/iPr) residues are likely protonated under the assay conditions used.
