Lysine‐241 Has a Role in Coupling 2OG Turnover with Substrate Oxidation During KDM4‐Catalysed Histone Demethylation |
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| Authors: | Dr Rebecca L Hancock Dr Martine I Abboud Dr Tristan J Smart Dr Emily Flashman Dr Akane Kawamura Prof Christopher J Schofield Dr Richard J Hopkinson |
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| Affiliation: | 1. Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, UK;2. Leicester Institute of Chemical and Structural Biology, University of Leicester, Leicester, UK |
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| Abstract: | The JmjC histone lysyl demethylases (KDMs) play important roles in modulating histone methylation states and have the potential to be regulated by oxygen availability. Lys241 of the KDM4 subfamily is proposed to be important in oxygen binding by KDM4A. We report evidence that, although Lys241 is unlikely to be directly involved in oxygen binding, it has an important role in coupling 2‐oxoglutarate cosubstrate oxidation with lysine demethylase activity. The results suggest that compounds promoting the uncoupling of substrate oxidation are of interest as JmjC‐KDM inhibitors. |
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