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PDBsum entry 1v97
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Oxidoreductase
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PDB id
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1v97
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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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The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition.
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Authors
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K.Okamoto,
K.Matsumoto,
R.Hille,
B.T.Eger,
E.F.Pai,
T.Nishino.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
7931-7936.
[DOI no: ]
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PubMed id
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Abstract
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Molybdenum is widely distributed in biology and is usually found as a
mononuclear metal center in the active sites of many enzymes catalyzing oxygen
atom transfer. The molybdenum hydroxylases are distinct from other biological
systems catalyzing hydroxylation reactions in that the oxygen atom incorporated
into the product is derived from water rather than molecular oxygen. Here, we
present the crystal structure of the key intermediate in the hydroxylation
reaction of xanthine oxidoreductase with a slow substrate, in which the
carbon-oxygen bond of the product is formed, yet the product remains complexed
to the molybdenum. This intermediate displays a stable broad charge-transfer
band at approximately 640 nm. The crystal structure of the complex indicates
that the catalytically labile Mo-OH oxygen has formed a bond with a carbon atom
of the substrate. In addition, the MoS group of the oxidized enzyme has become
protonated to afford Mo-SH on reduction of the molybdenum center. In contrast to
previous assignments, we find this last ligand at an equatorial position in the
square-pyramidal metal coordination sphere, not the apical position. A water
molecule usually seen in the active site of the enzyme is absent in the present
structure, which probably accounts for the stability of this intermediate toward
ligand displacement by hydroxide.
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Figure 4.
Fig. 4. Stereo representation of the structure in the
active site of XDH with bound FYX-051. FYX-051 (magenta),
molybdopterin (cyan), and catalytically important amino acid
residues (CPK-atom colored) are illustrated as stick models on a
ribbon model background.
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Figure 7.
Fig. 7. Proposed mechanism initiated by base-assisted
nucleophilic attack of Mo--OH on heterocycles, with subsequent
hydride transfer to produce the reaction intermediate (c) whose
structure has been analyzed in this report. The subsequent
oxidation occurs via d or/and e with varying ratio depending on
the substrate used.
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