Fe2OGdependent

Fe2OGdependent refers to the family of non-heme iron(II)/2-oxoglutarate-dependent dioxygenases, a large and diverse group of enzymes that catalyze oxidative reactions by using Fe(II) and 2-oxoglutarate (2OG) as co-substrates and molecular oxygen as the oxidant. These enzymes can hydroxylate C–H bonds, desaturate substrates, epoxidize alkenes, demethylate nucleic acids and proteins, and in some cases effect halogenation in the presence of halide.

A common active-site feature is the facial triad consisting of two histidines and a carboxylate residue (aspartate or glutamate) that coordinate the Fe(II) center. 2OG binds to Fe(II) and, with substrate and O2, is decarboxylated to succinate and CO2. This reaction facilitates the formation of a high-valent Fe(IV)=O species that abstracts a hydrogen atom from the substrate, enabling rebound hydroxylation or other oxidative outcomes. In certain enzymes, halide ions enable incorporation of halogens rather than hydroxyl groups under appropriate conditions.

Substrates for this superfamily are highly varied, including amino acids, nucleic acids, and diverse small molecules. Notable roles include oxygen sensing and hypoxia response via prolyl hydroxylases that regulate hypoxia-inducible factor (HIF); DNA repair and demethylation through AlkB-family demethylases and the JmjC-domain and TET family of demethylases; and various biosynthetic and detoxification steps across bacteria, plants, and animals.

Biochemical properties commonly observed include reliance on Fe(II) and 2OG, with sometimes a need for ascorbate to maintain the Fe(II) state. The Fe2OG-dependent enzymes are of significant biomedical and biotechnological interest, including targets for disease therapy and tools for epigenetic and metabolic studies.