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Title
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Tertiary structure of conotoxin GIIIA in aqueous solution.
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Authors
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J.M.Lancelin,
D.Kohda,
S.Tate,
Y.Yanagawa,
T.Abe,
M.Satake,
F.Inagaki.
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Ref.
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Biochemistry, 1991,
30,
6908-6916.
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PubMed id
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Abstract
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The three-dimensional structure of conotoxin GIIIA, an important constituent of
the venom from the marine hunting snail Conus geographus L., was determined in
aqueous solution by two-dimensional proton nuclear magnetic resonance and
simulated annealing based methods. On the basis of 162 assigned nuclear
Overhauser effect (NOE) connectivities obtained at the medium field strength
frequency of 400 MHz, 74 final distance constraints of sequential and tertiary
ones were derived and used together with 18 torsion angle (phi, chi 1)
constraints and 9 distance constraints derived from disulfide bridges. A total
of 32 converged structures were obtained from 200 runs of calculations. The
atomic root-mean-square (RMS) difference about the mean coordinate positions
(excluding the terminal residues 1 and 22) is 0.8 A for backbone atoms (N, C
alpha, C). Conotoxin GIIIA is characterized by a particular folding of the 22
amino acid peptidic chain, which is stabilized by three disulfide bridges
arranged in cage at the center of a discoidal structure of approximately 20-A
diameter. The seven cationic side chains of lysine and arginine residues project
radially into the solvent and form potential sites of interaction with the
skeletal muscle sodium channel for which the toxin is a strong inhibitor. The
present results provide a molecular basis to elucidate the remarkable
physiological properties of this neurotoxin.
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