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Lysine‐241 Has a Role in Coupling 2OG Turnover with Substrate Oxidation During KDM4‐Catalysed Histone Demethylation
Author(s) -
Hancock Rebecca L.,
Abboud Martine I.,
Smart Tristan J.,
Flashman Emily,
Kawamura Akane,
Schofield Christopher J.,
Hopkinson Richard J.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800002
Subject(s) - demethylase , demethylation , lysine , histone , biochemistry , methylation , chemistry , substrate (aquarium) , cofactor , acetylation , subfamily , biology , enzyme , amino acid , dna methylation , dna , gene expression , ecology , gene
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.