Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases.
Bottom Line: Subsequently, they have been shown to catalyze N-demethylation (via hydroxylation) of N(ϵ)-methylated histone lysyl residues, as well as hydroxylation of multiple other residues.Recent work has identified roles for 2OG oxygenases in the modification of translation-associated proteins, which in some cases appears to be conserved from microorganisms through to humans.Here we give an overview of protein hydroxylation catalyzed by 2OG oxygenases, focusing on recent discoveries.
Affiliation: From the Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, United Kingdom.Show MeSH
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Mentions: In addition to the roles associated with protein modification, 2OG oxygenases function in fatty acid metabolism, carnitine biosynthesis, and phytanic acid catabolism, as well as in DNA and mRNA repair, regulation, and modification (6). 2OG oxygenases employ a conserved mechanism in which sequential binding of 2OG to the active site is followed by that of substrate and then oxygen (4, 7). Oxidative decarboxylation of 2OG yields a ferryl intermediate (FeIV=O), which reacts with the substrate to effect 2-electron oxidation, normally hydroxylation (Fig. 1A). N-Methyl demethylation proceeds via initial hydroxylation of the methyl group to form a hemiaminal intermediate, which fragments to give formaldehyde and the demethylated product.
Affiliation: From the Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, United Kingdom.