Figure 1. 2-HG Is a Competitive Inhibitor of α-KG for Histone Demethylases.
(A) 2-HG inhibits Caenorhabditis elegans KDM7A demethylase activity. CeKDM7A activities toward H3K9me2 and H3K27me2 peptides were assayed in the presence of increasing concentrations of either D-2-HG or L-2-HG as indicated. The demethylated products were analyzed by mass spectrometry (left) and mean activity values of duplicated assays, represented by percentage of remaining methylated peptides (right), are shown. Error bars represent ± standard deviation (SD) for triplicate experiments.
(B) α-KG rescues 2-HG inhibition of CeKDM7A demethylase activity. Error bars represent ± SD for triplicate experiments.
(C) 2-HG inhibits human JHDM1A/KDM2A demethylase activity. Purified recombinant JHDM1A demethylase activity was assayed in the presence of various concentrations of D-2-HG and L-2-HG as indicated.
(D) α-KG reverses the inhibitory effect of D-2-HG on JHDM1A. JHDM1A activity was assayed in the presence of 50 mM D-2-HG and various concentrations of α-KG.
See also Figure S1.