PROSITE documentation PDOC51471

Fe(2+) 2-oxoglutarate dioxygenase domain profile

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 cosubstrate 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) α [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 (see <PDOC00165>). The eukaryotic and bacterial protein AlkB that also shows this structural domain is involved in DNA-repair [1,4].

The Fe(2+) 2OG dioxygenase domain has a conserved β-barrel structure (see <PDB:2G19>) [2], which forms a double-stranded β-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, which for most of these enzymes is 2OG, but e.g. not for IPNS.

Some proteins known to contain a Fe(2+) 2OG dioxygenase domain:

• Eukaryotic prolyl 4-hydroxylase subunit α-2 (EC 1.14.11.2), which catalyses the post-translational formation of 4-hydroxyproline in collagens and other proteins.
• Metazoan procollagen-lysine,2-oxoglutarate 5-dioxygenase (EC 1.14.11.4), which forms hydroxylysine residues in collagen type IV (see <PDOC01028>).
• Eukaryotic and bacterial α-ketoglutarate-dependent dioxygenase AlkB (EC 1.14.11.-), a DNA repair enzyme that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation.
• Vertebrate prolyl 3-hydroxylases (EC 1.14.11.7) of the leprecan family, which catalyse the post-translational formation of 3-hydroxyproline in collagens.
• Actinobacterial and fungal isopenicillin N synthase (IPNS) (EC 1.21.3.1), implicated in antibiotic biosynthesis (see <PDOC00165>).
• Actinobacterial and fungal deacetoxycephalosporin C synthase (DAOCS) (EC 1.14.20.1) and deacetoxycephalosporin C hydroxylase (DACS) (EC 1.14.11.26), which are implicated in antibiotic biosynthesis (see <PDOC00165>).
• Enterobacterial PKHD (prolyl/lysyl hydroxylase)-type hydroxylase ybiX (EC 1.14.11.-).
• Viral RNA-directed RNA polymerase (EC 2.7.7.48).
• Plant gibberellin 2-β-dioxygenases (EC 1.14.11.13) of the GA2OX subfamily of gibberellin (GAs) catabolic enzymes, which play a central role in plant development.
• Plant gibberellin 3-β-dioxygenases (EC 1.14.11.15) of the GA3OX subfamily.
• Plant flavone synthase (EC 1.14.11.22), flavonol synthase/flavanone 3-hydroxylase (EC 1.14.11.23, EC 1.14.11.9) and naringenin,2-oxoglutarate 3-dioxygenase (EC 1.14.11.9).
• Plant leucoanthocyanidin dioxygenase (LDOX) (EC 1.14.11.19) and deacetoxyvindoline 4-hydroxylase (EC 1.14.11.20).
• Plant 2'-deoxymugineic-acid 2'-dioxygenase (EC 1.14.11.24), mugineic-acid 3-dioxygenase (EC 1.14.11.25) and hyoscyamine 6-dioxygenase (EC 1.14.11.11).
• Plant 1-aminocyclopropane-1-carboxylate oxidases (ACC oxidases) (EC 1.14.17.4), which are ethylene-forming enzymes.
• Plant S-norcoclaurine synthase 1 (CjNCS1) (EC 4.2.1.78), involved in the biosynthesis of the common precursor of all benzylisoquinoline alkaloids such as morphine, sanguinarine, codeine or berberine.

The profile we developed covers the entire Fe(2+) 2OG dioxygenase domain.