Structure and mechanism of mouse cysteine dioxygenase

Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3084-9. doi: 10.1073/pnas.0509262103. Epub 2006 Feb 21.


Cysteine dioxygenase (CDO) catalyzes the oxidation of l-cysteine to cysteine sulfinic acid. Deficiencies in this enzyme have been linked to autoimmune diseases and neurological disorders. The x-ray crystal structure of CDO from Mus musculus was solved to a nominal resolution of 1.75 Angstroms. The sequence is 91% identical to that of a human homolog. The structure reveals that CDO adopts the typical beta-barrel fold of the cupin superfamily. The NE2 atoms of His-86, -88, and -140 provide the metal binding site. The structure further revealed a covalent linkage between the side chains of Cys-93 and Tyr-157, the cysteine of which is conserved only in eukaryotic proteins. Metal analysis showed that the recombinant enzyme contained a mixture of iron, nickel, and zinc, with increased iron content associated with increased catalytic activity. Details of the predicted active site are used to present and discuss a plausible mechanism of action for the enzyme.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cysteine Dioxygenase / chemistry*
  • Cysteine Dioxygenase / genetics
  • Cysteine Dioxygenase / metabolism*
  • Humans
  • Kinetics
  • Ligands
  • Metals / chemistry
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Folding
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Structure-Activity Relationship


  • Ligands
  • Metals
  • Cysteine Dioxygenase

Associated data

  • PDB/2ATF