Molecular basis of sulfite oxidase deficiency from the structure of sulfite oxidase.
The molybdenum-containing enzyme sulfite oxidase catalyzes the conversion of sulfite to sulfate, the terminal step in the oxidative degradation of cysteine and methionine. Deficiency of this enzyme in humans usually leads to major neurological abnormalities and early death. The crystal structure of chicken liver sulfite oxidase at 1.9 A resolution reveals that each monomer of the dimeric enzyme consists of three domains. At the active site, the Mo is penta-coordinated by three sulfur ligands, one oxo group, and one water/hydroxo. A sulfate molecule adjacent to the Mo identifies the substrate binding pocket. Four variants associated with sulfite oxidase deficiency have been identified: two mutations are near the sulfate binding site, while the other mutations occur within the domain mediating dimerization.
Kisker
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Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA. kisker@citray.caltech.edu
Schindelin
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H
Pacheco
A
A
Wehbi
W A
WA
Garrett
R M
RM
Rajagopalan
K V
KV
Enemark
J H
JH
Rees
D C
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002645:Chickens; D019281:Dimerization; D005347:Fibroblasts / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics; D017354:Point Mutation; D011487:Protein Conformation; D017510:Protein Folding; D016415:Sequence Alignment
D050862:Oxidoreductases Acting on Sulfur Group Donors