Enzymes with the Fe(2+) and 2-oxoglutarate (2OG)-dependent dioxygenase domain typically catalyse the oxidation of an organic substrate using a dioxygen molecule, mostly by using ferrous iron as the active site cofactor and 2OG as a co-substrate which is decarboxylated to succinate and CO2 [1]. Iron 2OG dioxygenase domain proteins are widespread among eukaryotes and bacteria. In metazoans, prolyl hydroxylases containing the domain act as oxygen sensors and catalyse the hydroxylation of conserved prolyl residues in hypoxia-inducible transcription factor (HIF) alpha [2, 3]. In plants, Fe(II) 2OG dioxygenase domain enzymes catalyse the formation of plant hormones, such as ethylene, gibberellins, anthocyanidins and pigments such as flavones. In bacteria and fungi Fe(II) 2OG dioxygenase domain enzymes participate in the biosynthesis of antibiotics such as penicillin and cephalosporin. The eukaryotic and bacterial protein AlkB that also shows this structural domain is involved in DNA-repair [4, 4].

The iron 2OG dioxygenase domain has a conserved beta-barrel structure [5], which forms a double-stranded beta-helix core fold that forms the predominant class of the cupin superfamily ('cupa' means a small barrel in Latin) [5]. Two histidines and an aspartate residue catalytically bind a metal ion, in general iron but in some cases another metal, directly involved in catalysis. A conserved arginine or lysine residue further near the C-terminal part acts as the basic residue that interacts with the acidic substrate.

1. The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases. Genome Biol. 2, RESEARCH0007
2. Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2). Proc. Natl. Acad. Sci. U.S.A. 103, 9814-9
3. Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing. Cell. Mol. Life Sci. 66, 3539-54
4. Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria. Nucleic Acids Res. 37, 7124-36
5. Cupins: the most functionally diverse protein superfamily? Phytochemistry 65, 7-17

Enzymes with the Fe(2+) and 2-oxoglutarate (2OG)-dependent dioxygenase domain typically catalyse
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