Recapture of [S]-allantoin, the product of the two-step degradation of uric acid, by urate oxidase.
Urate oxidase from Aspergillus flavus catalyzes the degradation of uric acid to [S]-allantoin through 5-hydroxyisourate as a metastable intermediate. The second degradation step is thought either catalyzed by another specific enzyme, or spontaneous. The structure of the enzyme was known at high resolution by X-ray diffraction of I222 crystals complexed with a purine-type inhibitor (8-azaxanthin). Analyzing the X-ray structure of urate oxidase treated with an excess of urate, the natural substrate, shows unexpectedly that the active site recaptures [S]-allantoin from the racemic end product of a second degradation step.
Laboratoire de cristallographie et RMN biologiques (UMR 8015 CNRS), Faculté de Pharmacie, Université Paris V, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Laure
L
Gabison
Mohamed
M
Chiadmi
Nathalie
N
Colloc'h
Bertrand
B
Castro
Mohamed
M
El Hajji
Thierry
T
Prangé
D000481:Allantoin / Q000378:metabolism*; D001231:Aspergillus flavus / Q000201:enzymology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D014503:Urate Oxidase / Q000378:metabolism*; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism*
D011994:Recombinant Proteins; D014527:Uric Acid; D000481:Allantoin; D014503:Urate Oxidase