Open AccessStructure and mechanism of mouse cysteine dioxygenase
Author(s) -
Jason G. McCoy,
L.J. Bailey,
E. Bitto,
C.A. Bingman,
David J. Aceti,
Brian G. Fox,
George N. Phillips
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0509262103
Subject(s) - cysteine , chemistry , enzyme , biochemistry , active site , recombinant dna , stereochemistry , peptide sequence , dioxygenase , protein structure , amino acid , cysteine metabolism , binding site , gene
Cysteine dioxygenase (CDO) catalyzes the oxidation ofl -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 fromMus musculus was solved to a nominal resolution of 1.75 Å. The sequence is 91% identical to that of a human homolog. The structure reveals that CDO adopts the typical β-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.