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PDBsum entry 2jj2
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Contents |
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(+ 0 more)
487 a.a.
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(+ 0 more)
467 a.a.
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167 a.a.
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References listed in PDB file
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Key reference
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Title
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Mechanism of inhibition of bovine f1-Atpase by resveratrol and related polyphenols.
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Authors
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J.R.Gledhill,
M.G.Montgomery,
A.G.Leslie,
J.E.Walker.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
13632-13637.
[DOI no: ]
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PubMed id
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Abstract
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The structures of F(1)-ATPase from bovine heart mitochondria inhibited with the
dietary phytopolyphenol, resveratrol, and with the related polyphenols quercetin
and piceatannol have been determined at 2.3-, 2.4- and 2.7-A resolution,
respectively. The inhibitors bind to a common site in the inside surface of an
annulus made from loops in the three alpha- and three beta-subunits beneath the
"crown" of beta-strands in their N-terminal domains. This region of
F(1)-ATPase forms a bearing to allow the rotation of the tip of the
gamma-subunit inside the annulus during catalysis. The binding site is a
hydrophobic pocket between the C-terminal tip of the gamma-subunit and the
beta(TP) subunit, and the inhibitors are bound via H-bonds mostly to their
hydroxyl moieties mediated by bound water molecules and by hydrophobic
interactions. There are no equivalent sites between the gamma-subunit and either
the beta(DP) or the beta(E) subunit. The inhibitors probably prevent both the
synthetic and hydrolytic activities of the enzyme by blocking both senses of
rotation of the gamma-subunit. The beneficial effects of dietary resveratrol may
derive in part by preventing mitochondrial ATP synthesis in tumor cells, thereby
inducing apoptosis.
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Figure 1.
Fig. 1. Structures of polyphenol inhibitors of bovine
F[1]-ATPase. (I) Resveratrol. (II) Piceatannol. (III) Quercetin.
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Figure 3.
Fig. 3. Comparison of the modes of binding to bovine
F[1]-ATPase of piceatannol and quercetin with that of
resveratrol. (A) Major binding modes of resveratrol (green) and
piceatannol (gray). (B) Major binding mode of resveratrol
(green) and cis-quercetin (gray).
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