PROSITE documentation PDOC51471

Fe(2+) 2-oxoglutarate dioxygenase domain profile





Description

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.

Last update:

December 2009 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

FE2OG_OXY, PS51471; Fe(2+) 2-oxoglutarate dioxygenase domain profile  (MATRIX)


References

1AuthorsAravind L., Koonin E.V.
TitleThe DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases.
SourceGenome Biol. 2:RESEARCH0007-RESEARCH0007(2001).
PubMed ID11276424

2AuthorsMcDonough M.A., Li V., Flashman E., Chowdhury R., Mohr C., Lienard B.M., Zondlo J., Oldham N.J., Clifton I.J., Lewis J., McNeill L.A., Kurzeja R.J., Hewitson K.S., Yang E., Jordan S., Syed R.S., Schofield C.J.
TitleCellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2).
SourceProc. Natl. Acad. Sci. U.S.A. 103:9814-9819(2006).
PubMed ID16782814
DOI10.1073/pnas.0601283103

3AuthorsWebb J.D., Coleman M.L., Pugh C.W.
TitleHypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing.
SourceCell. Mol. Life Sci. 0:0-0(2009).
PubMed ID19756382
DOI10.1007/s00018-009-0147-7

4Authorsvan den Born E., Bekkelund A., Moen M.N., Omelchenko M.V., Klungland A., Falnes P.O.
TitleBioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria.
SourceNucleic Acids Res. 0:0-0(2009).
PubMed ID19786499
DOI10.1093/nar/gkp774

5AuthorsDunwell J.M., Purvis A., Khuri S.
TitleCupins: the most functionally diverse protein superfamily?
SourcePhytochemistry 65:7-17(2004).
PubMed ID14697267



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)