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PDBsum entry 2ahk
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Oxidoreductase/metal transport
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PDB id
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2ahk
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References listed in PDB file
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Key reference
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Title
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Crystallographic evidence that the dinuclear copper center of tyrosinase is flexible during catalysis.
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Authors
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Y.Matoba,
T.Kumagai,
A.Yamamoto,
H.Yoshitsu,
M.Sugiyama.
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Ref.
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J Biol Chem, 2006,
281,
8981-8990.
[DOI no: ]
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PubMed id
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Abstract
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At high resolution, we determined the crystal structures of copper-bound and
metal-free tyrosinase in a complex with ORF378 designated as a "caddie" protein
because it assists with transportation of two CuII ions into the tyrosinase
catalytic center. These structures suggest that the caddie protein covers the
hydrophobic molecular surface of tyrosinase and interferes with the binding of a
substrate tyrosine to the catalytic site of tyrosinase. The caddie protein,
which consists of one six-strandedbeta-sheet and one alpha-helix, has no
similarity with all proteins deposited into the Protein Data Bank. Although
tyrosinase and catechol oxidase are classified into the type 3 copper protein
family, the latter enzyme lacks monooxygenase activity. The difference in
catalytic activity is based on the structural observations that a large vacant
space is present just above the active center of tyrosinase and that one of the
six His ligands for the two copper ions is highly flexible. These structural
characteristics of tyrosinase suggest that, in the reaction that catalyzes the
ortho-hydroxylation of monophenol, one of the two Cu(II) ions is coordinated by
the peroxide-originated oxygen bound to the substrate. Our crystallographic
study shows evidence that the tyrosinase active center formed by dinuclear
coppers is flexible during catalysis.
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Figure 5.
FIGURE 5. Structural similarity. A, stereo representation
of the superposition of tyrosinase and structurally homologous
proteins, potato catechol oxidase (Protein Data Bank code 1BT1)
and octopus hemocyanin (Protein Data Bank code 1JS8). Red, blue,
and green indicate the backbone traces of tyrosinase, catechol
oxidase, and hemocyanin, respectively. The yellow sphere
indicates the two copper ions in the catalytic center. To
emphasize similarity, the C-terminal domain of hemocyanin is
omitted from the figure. B, stereo view of the superposition of
ORF378 and the SH2 domain in the growth factor-bound protein 2
(Protein Data Bank code 1GRI). Red and blue indicate the
backbone trace of ORF378 and the SH2 domain in the growth
factor-bound protein 2, respectively.
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Figure 9.
FIGURE 9. Structure-based catalytic mechanism of
tyrosinase. The oxy form of tyrosinase catalyzes the conversion
of monophenol to the corresponding quinone through the
ortho-diphenol formation. In this scheme, His^54 is released
from the Cu^A site, resulting in the formation of the bidentate
intermediate. The met and oxy forms of tyrosinase can catalyze
the conversion of ortho-diphenol to the corresponding quinone.
This reaction should progress similarly to that of catechol
oxidase.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
8981-8990)
copyright 2006.
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