Structure and mechanism of mouse cysteine dioxygenase.

TitleStructure and mechanism of mouse cysteine dioxygenase.
Publication TypeJournal Article
Year of Publication2006
AuthorsMcCoy JG, Bailey LJ, Bitto E, Bingman CA, Aceti DJ, Fox BG, Phillips GN
JournalProc Natl Acad Sci U S A
Volume103
Issue9
Pagination3084-9
Date Published2006 Feb 28
ISSN0027-8424
KeywordsAmino Acid Sequence, Animals, Binding Sites, Conserved Sequence, Crystallography, X-Ray, Cysteine Dioxygenase, Humans, Kinetics, Ligands, Metals, Mice, Models, Molecular, Molecular Sequence Data, Protein Folding, Protein Structure, Tertiary, Sequence Alignment, Structure-Activity Relationship
Abstract

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.

DOI10.1073/pnas.0509262103
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID16492780
PubMed Central IDPMC1413891
Grant ListGM-50853 / GM / NIGMS NIH HHS / United States
P50 GM 64598 / GM / NIGMS NIH HHS / United States
T15 LM007359 / LM / NLM NIH HHS / United States
U54 GM 074901 / GM / NIGMS NIH HHS / United States
Y1-CO-1020 / CO / NCI NIH HHS / United States
Y1-GM-1104 / GM / NIGMS NIH HHS / United States