Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases

Curr Opin Struct Biol. 2012 Dec;22(6):691-700. doi: 10.1016/ Epub 2012 Nov 9.


2-Oxoglutarate (2OG) and ferrous iron dependent oxygenases catalyze two-electron oxidations of a range of small and large molecule substrates, including proteins/peptides/amino acids, nucleic acids/bases, and lipids, as well as natural products including antibiotics and signaling molecules. 2OG oxygenases employ variations of a core double-stranded β-helix (DSBH; a.k.a. jelly-roll, cupin or jumonji C (JmjC)) fold to enable binding of Fe(II) and 2OG in a subfamily conserved manner. The topology of the DSBH limits regions directly involved in substrate binding: commonly the first, second and eighth strands, loops between the second/third and fourth/fifth DSBH strands, and the N-terminal and C-terminal regions are involved in primary substrate, co-substrate and cofactor binding. Insights into substrate recognition by 2OG oxygenases will help to enable selective inhibition and bioengineering studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Oxygenases / antagonists & inhibitors
  • Oxygenases / chemistry*
  • Oxygenases / genetics
  • Oxygenases / metabolism*
  • Protein Binding
  • Protein Engineering
  • Protein Structure, Secondary


  • Enzyme Inhibitors
  • Oxygenases