Demethylases are enzymes that remove methyl (CH3) groups from nucleic acids, proteins (particularly histones), and other molecules.
Demethylases are important epigenetic proteins, as they are responsible for transcriptional regulation of the genome by controlling the methylation of DNA and histones, and by extension, the chromatin state at specific gene loci.
[2] Two main classes of histone lysine demethylases exist, defined by their mechanisms: flavin adenine dinucleotide (FAD)-dependent amine oxidases and α-ketoglutarate-dependent hydroxylases.
Phosphorylation of CheB protein enhances its catalytic MCP demethylating activity resulting in adaption of the cell to environmental stimuli.
CheB is more specifically termed a methylesterase, as it removes methyl groups from methylglutamate residues located on the MCPs through hydrolysis, producing glutamate accompanied by the release of methanol.
Lysine demethylatiuon mechanisms of histone lysine demethylase 1A (KDM1A) and the JmjC-domain-containing histone lysine demethylases (JHDMs). Both mechanisms involve the oxidation of a methyl group (with
FAD
or
α-ketoglutarate
as cofactors) followed by the elimination of
formaldehyde
. The mechanism of KDM1A and KDM1B is dependent on the formation of an iminium intermediate and therefore they may only demethylate mono- and dimethylated lysine substrates.
Structure of JmJDA (coordinates from PDB file:2UXX); Some domains from above are highlighted: JmJ(N-terminus, red; C-terminus, yellow), Zinc finger domain (light purple), Beta-hairpin (light blue), and mixed domain linker (green).
Structure of KDM1A (coordinates from PDB file:2Z5U)
Cartoon representation of the molecular structure of protein registered with 1A2O pdb code.
Chemotaxis signalling. Chemoattractants or repellents are sensed by transmembrane receptors. Note the role of CheB (B) in demethylation of MCP receptors.
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