Crystal Structure of the protein drug urate oxidase-inhibitor complex at 2.05 Å resolution
- 1 November 1997
- journal article
- research article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 4 (11) , 947-952
- https://doi.org/10.1038/nsb1197-947
Abstract
The gene coding for urate oxidase, an enzyme that catalyzes the oxidation of uric acid to allantoin, is inactivated in humans. Consequently, urate oxidase is used as a protein drug to overcome severe disorders induced by uric acid accumulation. The structure of the active homotetrameric enzyme reveals the existence of a small architectural domain that we call T-fold (for tunnelling-fold) domain. It assembles to form a perfect unusual dimeric α8β16 barrel. Urate oxidase may be the archetype of an expanding new family of tunnel-shaped proteins that now has three members; tetrahydropterin synthase, GTP cyclohydrolase I and urate oxidase. The structure of the active site of urate oxidase around the 8-azaxanthine inhibitor reveals an original mechanism of oxidation that does not require any ions or prosthetic groups.Keywords
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