Structure and mechanism of mouse cysteine dioxygenase.

Jason G McCoy, Lucas J Bailey, Eduard Bitto, Craig A Bingman, David J Aceti, Brian G Fox, George N Phillips

Center for Eukaryotic Structural Genomics and Department of Biochemistry, University of Wisconsin, Madison, 53706-1544, USA.

Proceedings of the National Academy of Sciences of the United States of America 2006 Feb 28

filter terms:

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.

Citation

Jason G McCoy, Lucas J Bailey, Eduard Bitto, Craig A Bingman, David J Aceti, Brian G Fox, George N Phillips. Structure and mechanism of mouse cysteine dioxygenase. Proceedings of the National Academy of Sciences of the United States of America. 2006 Feb 28;103(9):3084-9