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PDBsum entry 1jro
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Oxidoreductase
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PDB id
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1jro
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structures of the active and alloxanthine-Inhibited forms of xanthine dehydrogenase from rhodobacter capsulatus.
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Authors
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J.J.Truglio,
K.Theis,
S.Leimkühler,
R.Rappa,
K.V.Rajagopalan,
C.Kisker.
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Ref.
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Structure, 2002,
10,
115-125.
[DOI no: ]
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PubMed id
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Abstract
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Xanthine dehydrogenase (XDH), a complex molybdo/iron-sulfur/flavoprotein,
catalyzes the oxidation of hypoxanthine to xanthine followed by oxidation of
xanthine to uric acid with concomitant reduction of NAD+. The 2.7 A resolution
structure of Rhodobacter capsulatus XDH reveals that the bacterial and bovine
XDH have highly similar folds despite differences in subunit composition. The
NAD+ binding pocket of the bacterial XDH resembles that of the dehydrogenase
form of the bovine enzyme rather than that of the oxidase form, which reduces
O(2) instead of NAD+. The drug allopurinol is used to treat XDH-catalyzed uric
acid build-up occurring in gout or during cancer chemotherapy. As a hypoxanthine
analog, it is oxidized to alloxanthine, which cannot be further oxidized but
acts as a tight binding inhibitor of XDH. The 3.0 A resolution structure of the
XDH-alloxanthine complex shows direct coordination of alloxanthine to the
molybdenum via a nitrogen atom. These results provide a starting point for the
rational design of new XDH inhibitors.
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Figure 6.
Figure 6. Schematic Representation of Protein-Moco
InteractionsDashed lines indicate hydrogen bonds. In addition,
the aromatic side chain of Phe-B228 stacks with the pterin rings
(not shown).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2002,
10,
115-125)
copyright 2002.
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