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Crystal Structure of the protein drug urate oxidase-inhibitor complex at 2.05 Å resolution

Nature Structural Biology volume 4, pages 947–952 (1997)Cite this article

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.

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Authors and Affiliations

  1. Systèmes Moleculaires et Biologic Structurale, Laboratoire de Minéralogie-Cristallographie, CNRS URA09, Université Paris VI et Paris VII, case 115,4 place Jussieu, 75252, Paris, cedex 05, France

    Nathalie Colloc'h, Bernard Bachet, Guillaume L'Hermite & Jean-Paul Mornon

  2. SANOFI Chimie, route d'Avignon, 30390, Aramon, France

    Mohamed El Hajji

  3. LURE, Université Paris-Sud, Bat. 209d, 91405, Orsay cedex, France

    Marc Schiltz & Thierry Prangé

  4. Chimie Structurale Biomoléculaire, CNRS URA1430, 93017, Bobigny cedex, France

    Thierry Prangé

  5. SANOFI Chimie, 82 avenue Raspail, 94255, Gentilly cedex, France

    Bertrand Castro

Authors
  1. Nathalie Colloc'h
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  2. Mohamed El Hajji
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  4. Guillaume L'Hermite
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  8. Jean-Paul Mornon
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Colloc'h, N., Hajji, M., Bachet, B. et al. Crystal Structure of the protein drug urate oxidase-inhibitor complex at 2.05 Å resolution. Nat Struct Mol Biol 4, 947–952 (1997). https://doi.org/10.1038/nsb1197-947

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