JMJD2A in Complex with H3K9me3

Description

JMJD2A is a histone demethylase (HDM) belonging to the JmjC family and catalyzing the demethylation of H3K9me2/3 and H3K36me2/3 which can lead to transcriptional activation. The JmjC domain of JMJD2A (shown as a cartoon) has a beta-barrel fold and includes an Fe(II) centre and binding sites for its substrates H3K9me3 and alpha-ketoglutarate. Crystallography of human JMJD2A in complex with H3K9me3 reveals histone substrates are deposited into the active site through a network of hydrogen bonds (Couture et al., 2007). In the binding pocket carbon-oxygen (CH···O) hydrogen bonds positions one of the trimethyllysine methyl groups near the Fe(II) centre for demethylation. Mutations of residues in the binding pocket abrogates demethylase activity, however S288A substitution enhances preference for dimethylated over trimethylated lysine and has been proposed to be responsible for the methylation-state specificity of JMJD2A (Couture et al., 2007). References: https://doi.org/10.1038/nsmb1273