JMJD2A: a molecule that doesn't play games!

3D Model

JMJD2A is a molecule that demethylates di- and tri-methylated lysine-9 and lysine-36 in histone H3, acting as an eraser and making the associated genes more accessible for transcription. Its catalytic activity is in its substrate binding cleft. This model includes the molecule in complex with Ni2+ (normally it is in complex with Fe (II)), ɑ-ketoglutarate and a short peptide representative of H3K9me3 with some side-residues attached as they would be on the histone tail. On this tour, we first will get a global picture of the molecule. Then, we show the structures of the molecule that have a role in substrate recognition and after this we go into the active site itself. The tour is finished up with how demethylation occurs and an explanation of where the enzyme gains its specificity.

Keep all limbs inside the carriage and strap yourself in for an adventure! Main source (given): https://doi.org/10.1038/nsmb1273

Other sources: https://doi.org/10.1002/chem.20160421, https://doi.org/10.1021/acs.jpcb.9b06064