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PDBsum entry 1tyr
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Retinol-binding
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PDB id
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1tyr
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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 of the transthyretin--Retinoic-Acid complex.
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Authors
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G.Zanotti,
M.R.D'Acunto,
G.Malpeli,
C.Folli,
R.Berni.
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Ref.
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Eur J Biochem, 1995,
234,
563-569.
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PubMed id
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Abstract
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Retinoids are quite insoluble and chemically unstable compounds in the aqueous
medium, such that natural retinoids need to be bound to specific
retinoid-binding proteins to be protected, solubilized and transported in body
fluids. All-trans retinoic acid exhibits a relatively high affinity for
thyroxine-binding transthyretin in vitro and this protein is a good candidate
for the transport of retinoic acid administered as pharmacological or antitumor
agent. To define structural features essential for the recognition by
transthyretin of a ligand which is structurally unrelated to thyroxine, we have
cocrystallized human transthyretin with retinoic acid and determined its
structure at 0.18-nm resolution. The retinoid fits into the two chemically
identical thyroxine-binding sites, which are located in the central channel that
runs through the tetrameric transthyretin. The cyclohexene ring of the bound
retinoid is innermost, occupying the same position of the phenolic ring of the
bound 3,3'-diiodo-L-thyronine, whereas the carboxylate group, like the same
group of the thyroid hormone, participates in an ionic interaction with the
Lys15 side chain at the entrance of the channel. Despite the fact that
transthyretin was cocrystallized with all-trans-retinoic acid, the isoprene
chain of the bound retinoid has been found in a non-extended conformation. This
feature, that allows the carboxylate to orient in a manner suitable for ion-pair
association with the Lys15 side chain, is attributable to the conversion of
all-trans-retinoic acid into cis-isomers or folded conformers. It is concluded
that the presence, in an essentially hydrophobic molecular core of the
appropriate size, of a negatively charged group at the correct position is a
crucial requirement for ligand-transthyretin recognition. Whereas the binding of
the ligand has no remarkable consequences for the protein structure,
all-trans-retinoic acid undergoes structural changes such as to interact
favorably with residues present in the thyroxine-binding sites, resembling
roughly the natural ligand.
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Secondary reference #1
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Title
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Crystallographic studies on complexes between retinoids and plasma retinol-Binding protein.
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Authors
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G.Zanotti,
M.Marcello,
G.Malpeli,
C.Folli,
G.Sartori,
R.Berni.
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Ref.
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J Biol Chem, 1994,
269,
29613-29620.
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PubMed id
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Secondary reference #2
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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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Secondary reference #3
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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 #4
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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 #5
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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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