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PDBsum entry 1thc
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Transport (thyroxine,retinol) in serum
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PDB id
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1thc
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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 structure determination at 2.3-A resolution of human transthyretin-3',5'-Dibromo-2',4,4',6-Tetrahydroxyaurone complex.
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Authors
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E.Ciszak,
V.Cody,
J.R.Luft.
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Ref.
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Proc Natl Acad Sci U S A, 1992,
89,
6644-6648.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of the complex of
3',5'-dibromo-2',4,4',6-tetrahydroxyaurone, a flavone derivative, with human
transthyretin (TTR), a serum thyroid hormone transport protein, has been
determined and refined to R = 17.9% for data to 2.3-A resolution and provides a
detailed description of a protein-bound flavonoid structure. This bromoaurone is
a potent competitor for thyroid hormone binding to TTR, a 54,980-dalton alpha 4
tetrameric protein of 222 molecular symmetry, as well as an inhibitor of
iodothyronine deiodinase. Crystals of the TTR-bromoaurone complex are
isomorphous to those of native TTR. Interpretation of difference Fourier
electron density maps revealed two binding modes for the bromoaurone in each of
the two independent binding sites of the TTR tetramer: deep in the channel near
Ser-117 (mode I) and near the channel entrance (mode II). None of the binding
modes can be fully occupied because of overlap between binding positions. A
statistical disorder for bromoaurone binding was also applied, as it binds along
the twofold crystallographic axis and does not possess such symmetry. The
binding of mode I and that of mode II were refined at half occupancy, resulting
in two molecules per tetramer. The bromoaurone binds in a nonplanar antiskewed
conformation. The molecular pattern for TTR binding consists of halogen groups
able to anchor between beta-sheets to form both hydrophobic and hydrophilic
contacts. Comparison of structural data for bromoaurone- and thyroxine-TTR
complexes indicates that bromoaurone binding mode I is 3 A deeper in the channel
and binding mode II is 4 A further from the channel center than thyroxine. The
bromoaurone binding observed in this TTR complex differs significantly from that
based upon computer modeling studies.
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Secondary reference #1
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Title
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Mechanism of molecular recognition. Structural aspects of 3,3'-Diiodo-L-Thyronine binding to human serum transthyretin.
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Authors
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A.Wojtczak,
J.Luft,
V.Cody.
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Ref.
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J Biol Chem, 1992,
267,
353-357.
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PubMed id
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Secondary reference #2
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Title
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Protein-Dna and protein-Hormone interactions in prealbumin: a model of the thyroid hormone nuclear receptor?
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Authors
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C.C.Blake,
S.J.Oatley.
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Ref.
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Nature, 1977,
268,
115-120.
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PubMed id
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Secondary reference #3
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Title
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Strjcture of human plasma prealbumin at 2-5 a resolution. A preliminary report on the polypeptide chain conformation, Quaternary structure and thyroxine binding.
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Authors
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C.C.Blake,
M.J.Geisow,
I.D.Swan,
C.Rerat,
B.Rerat.
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Ref.
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J Mol Biol, 1974,
88,
1.
[DOI no: ]
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PubMed id
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Figure 6.
FIG. 6. A stereo-view of the prealbumin tetramer down the molecular y'axis. N - residue 10;
C E reidue 126. T--- T represents the tw di-iodotyrosyl residues of thyroxine located on
the molecular c-axis.
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Figure 7.
FIG. 7. A stereo-view of the prealbumin tetramer looking down the molecular z-axis, shown
by the dot, with the molecular x' and y'-&is horizontal and vertical, respectively, The thyroxine
binding sites are superposed along the zaxis.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #4
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Title
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An X-Ray study of the subunit structure of prealbumin.
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Authors
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C.C.Blake,
I.D.Swan,
C.Rerat,
J.Berthou,
A.Laurent,
B.Rerat.
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Ref.
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J Mol Biol, 1971,
61,
217-224.
[DOI no: ]
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PubMed id
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Figure 1.
FIG. . The ymmetry relations of a) 222, (b) P212,2 and (c) 222 projectd own the c-axis.
he origin of 21212 has been hifted from ts onventional position to O,O,) to show its relation-
hip o I222 ore learly.
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The above figure is
reproduced from the cited reference
with permission from Elsevier
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