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PDBsum entry 3ld4
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Oxidoreductase
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PDB id
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3ld4
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References listed in PDB file
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Key reference
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Title
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Near-Atomic resolution structures of urate oxidase complexed with its substrate and analogues: the protonation state of the ligand.
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Authors
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L.Gabison,
M.Chiadmi,
M.El hajji,
B.Castro,
N.Colloc'H,
T.Prangé.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2010,
66,
714-724.
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PubMed id
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Abstract
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Urate oxidase (uricase; EC 1.7.3.3; UOX) from Aspergillus flavus catalyzes the
oxidation of uric acid in the presence of molecular oxygen to 5-hydroxyisourate
in the degradation cascade of purines; intriguingly, catalysis proceeds using
neither a metal ion (Fe, Cu etc.) nor a redox cofactor. UOX is a tetrameric
enzyme with four active sites located at the interface of two subunits; its
structure was refined at atomic resolution (1 A) using new crystal data in the
presence of xanthine and at near-atomic resolution (1.3-1.7 A) in complexes with
the natural substrate (urate) and two inhibitors: 8-nitroxanthine and 8-thiouric
acid. Three new features of the structural and mechanistic behaviour of the
enzyme were addressed. Firstly, the high resolution of the UOX-xanthine
structure allowed the solution of an old structural problem at a contact zone
within the tetramer; secondly, the protonation state of the substrate was
determined from both a halochromic inhibitor complex (UOX-8-nitroxanthine) and
from the H-atom distribution in the active site, using the structures of the
UOX-xanthine and the UOX-uric acid complexes; and thirdly, it was possible to
extend the general base system, characterized by the conserved catalytic triad
Thr-Lys-His, to a large water network that is able to buffer and shuttle protons
back and forth between the substrate and the peroxo hole along the reaction
pathway.
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