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PDBsum entry 1idh
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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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The solution structure of the complex formed between alpha-Bungarotoxin and an 18-Mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from torpedo californica.
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Authors
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H.Zeng,
L.Moise,
M.A.Grant,
E.Hawrot.
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Ref.
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J Biol Chem, 2001,
276,
22930-22940.
[DOI no: ]
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PubMed id
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Abstract
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The region encompassing residues 181-98 on the alpha1 subunit of the muscle-type
nicotinic acetylcholine receptor forms a major determinant for the binding of
alpha-neurotoxins. We have prepared an (15)N-enriched 18-amino acid peptide
corresponding to the sequence in this region to facilitate structural
elucidation by multidimensional NMR. Our aim was to determine the structural
basis for the high affinity, stoichiometric complex formed between this cognate
peptide and alpha-bungarotoxin, a long alpha-neurotoxin. Resonances in the
complex were assigned through heteronuclear and homonuclear NMR experiments, and
the resulting interproton distance constraints were used to generate ensemble
structures of the complex. Thr(8), Pro(10), Lys(38), Val(39), Val(40), and
Pro(69) in alpha-bungarotoxin and Tyr(189), Tyr(190), Thr(191), Cys(192),
Asp(195), and Thr(196) in the peptide participate in major intermolecular
contacts. A comparison of the free and bound alpha-bungarotoxin structures
reveals significant conformational rearrangements in flexible regions of
alpha-bungarotoxin, mainly loops I, II, and the C-terminal tail. Furthermore,
several of the calculated structures suggest that cation-pi interactions may be
involved in binding. The root mean square deviation of the polypeptide backbone
in the complex is 2.07 A. This structure provides, to date, the highest
resolution description of the contacts between a prototypic alpha-neurotoxin and
its cognate recognition sequence.
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Figure 8.
Fig. 8. Stereo view of the surface charge profile of the
Bgtx·  18-mer
complex. Surface charge potentials were calculated as described
under "Experimental Procedures." Blue regions show positive
charge, and red regions show negative charge. See Fig. 5B for
orientation. The figure was prepared using the program MOLMOL
(42).
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Figure 9.
Fig. 9. Orientation of a suggested Tyr190-Lys38 cation-
 interaction.
The two side chains are taken from one of the 20 ensemble
Bgtx· 18-mer
structures depicted in Fig. 5. a, the distance between the NZ of
Lys38 and the CE2 of Tyr190 is 5.49 Å; b, the distance
between the NZ of Lys38 and the CE1 of Tyr190 is 5.85 Å;
c, the distance between the CG of Tyr190 and the NZ of Lys38 is
5.53 Å.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2001,
276,
22930-22940)
copyright 2001.
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