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Title
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Crystal structure of the protein drug urate oxidase-inhibitor complex at 2.05 A resolution.
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Authors
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N.Colloc'h,
M.el Hajji,
B.Bachet,
G.L'Hermite,
M.Schiltz,
T.Prangé,
B.Castro,
J.P.Mornon.
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Ref.
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Nat Struct Biol, 1997,
4,
947-952.
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PubMed id
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Abstract
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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 alpha 8
beta 16 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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