Structure and mechanism of mouse cysteine dioxygenase.
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.
Center for Eukaryotic Structural Genomics and Department of Biochemistry, University of Wisconsin, Madison, 53706-1544, USA.
Jason G
JG
McCoy
Lucas J
LJ
Bailey
Eduard
E
Bitto
Craig A
CA
Bingman
David J
DJ
Aceti
Brian G
BG
Fox
George N
GN
Phillips
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D050558:Cysteine Dioxygenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008670:Metals / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D008024:Ligands; D008670:Metals; D050558:Cysteine Dioxygenase