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PDBsum entry 1e4z
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Bacteriophage hk022
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PDB id
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1e4z
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References listed in PDB file
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Key reference
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Title
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Structure of human transthyretin complexed with bromophenols: a new mode of binding.
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Authors
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M.Ghosh,
I.A.Meerts,
A.Cook,
A.Bergman,
A.Brouwer,
L.N.Johnson.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2000,
56,
1085-1095.
[DOI no: ]
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PubMed id
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Abstract
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The binding of two organohalogen substances, pentabromophenol (PBP) and
2,4,6-tribromophenol (TBP), to human transthyretin (TTR), a thyroid hormone
transport protein, has been studied by in vitro competitive binding assays and
by X-ray crystallography. Both compounds bind to TTR with high affinity, in
competition with the natural ligand thyroxine (T(4)). The crystal structures of
the TTR-PBP and TTR-TBP complexes show some unusual binding patterns for the
ligands. They bind exclusively in the 'reversed' mode, with their hydroxyl group
pointing towards the mouth of the binding channel and in planes approximately
perpendicular to that adopted by the T(4) phenolic ring in a TTR-T(4) complex, a
feature not observed before. The hydroxyl group in the ligands, which was
previously thought to be a key ingredient for a strong binding to TTR, does not
seem to play an important role in the binding of these compounds to TTR. In the
TTR-PBP complex, it is primarily the halogens which interact with the TTR
molecule and therefore must account for the strong affinity of binding. The
interactions with the halogens are smaller in number in TTR-TBP and there is a
decrease in affinity, even though the interaction with the hydroxyl group is
stronger than that in the TTR-PBP complex.
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Figure 1.
Figure 1 Schematic diagram of pentabromophenol,
2,4,6-tribromophenol and thyroxine.
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Figure 6.
Figure 6 Superposed view of thyroxine on the ligand PBP at the
TTR-PBP binding site. (a) In its principal binding mode PBP1,
the Br atoms Br2 and Br6 occupy the outer pockets of thyroxine
while (b) in the secondary binding mode PBP2, Br3 and Br5 are in
the inner pockets of the hormone. I atoms are shown in gold and
Br atoms are in rust red. The figures were created using the
program XOBJECTS (M. E. M. Noble, unpublished program).
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(2000,
56,
1085-1095)
copyright 2000.
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Secondary reference #1
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Title
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Antitermination in bacteriophage lambda. The structure of the n36 peptide-Boxb RNA complex.
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Authors
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M.Schärpf,
H.Sticht,
K.Schweimer,
M.Boehm,
S.Hoffmann,
P.Rösch.
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Ref.
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Eur J Biochem, 2000,
267,
2397-2408.
[DOI no: ]
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PubMed id
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Figure 6.
Fig. 6. Intermolecular NOEs between N36 peptide and boxB
RNA in the complex. NOEs between (A) the methyl group of Ala3
and nucleotides C2 and C3, (B1) the base of A7 (grey) and the
indole ring protons pf Trp18 (black) and (B2) additional NOEs of
this protons to the ribose of A7 (grey) and the side-chain
protons of Trp18 (black). Broken lines indicate resonances of
the boxB RNA and solid lines resonances of the peptide.
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Figure 8.
Fig. 8. The structure of the boxB RNAhairpin in the
complex. Twenty structures with the lowest energies of boxB RNA
are superimposed. The stem is coloured blue, the extruded
nucleotide (A9) is coloured yellow and the four nucleotides
forming the GNRA fold are shown in pink. In (A) only the heavy
atoms are shown to highlight stacking of A7, A8 and A10 onto the
3' strand of the stem; (B) is rotated by 90° to show the
GAAA tetraloop, the flipped out nucleotide and the formation of
a sheared base pair between G6 and A11 in more detail.
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The above figures are
reproduced from the cited reference
with permission from the Federation of European Biochemical Societies
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