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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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1 term
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Biological process
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pathogenesis
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1 term
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Biochemical function
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ion channel inhibitor activity
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1 term
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DOI no:
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Biochemistry
39:3908-3919
(2000)
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PubMed id:
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Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange.
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R.A.Atkinson,
B.Kieffer,
A.Dejaegere,
F.Sirockin,
J.F.Lefèvre.
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ABSTRACT
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omega-Conotoxin MVIIA is a 25-residue, disulfide-bridged polypeptide from the
venom of the sea snail Conus magus that binds to neuronal N-type calcium
channels. It forms a compact folded structure, presenting a loop between Cys8
and Cys15 that contains a set of residues critical for its binding. The loop
does not have a unique defined structure, nor is it intrinsically flexible.
Broadening of a subset of resonances in the NMR spectrum at low temperature,
anomalous temperature dependence of the chemical shifts of some resonances, and
exchange contributions to J(0) from (13)C relaxation measurements reveal that
conformational exchange affects the residues in this loop. The effects of this
exchange on the calculated structure of omega-conotoxin MVIIA are discussed. The
exchange appears to be associated with a change in the conformation of the
disulfide bridge Cys8-Cys20. The implications for the use of the
omega-conotoxins as a scaffold for carrying other functions is discussed.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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H.S.Smith,
and
T.R.Deer
(2009).
Safety and efficacy of intrathecal ziconotide in the management of severe chronic pain.
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| |
Ther Clin Risk Manag, 5,
521-534.
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N.L.Daly,
and
D.J.Craik
(2009).
Structural studies of conotoxins.
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IUBMB Life, 61,
144-150.
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T.F.Molinski,
D.S.Dalisay,
S.L.Lievens,
and
J.P.Saludes
(2009).
Drug development from marine natural products.
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| |
Nat Rev Drug Discov, 8,
69-85.
|
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A.Walewska,
J.J.Skalicky,
D.R.Davis,
M.M.Zhang,
E.Lopez-Vera,
M.Watkins,
T.S.Han,
D.Yoshikami,
B.M.Olivera,
and
G.Bulaj
(2008).
NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the mu-conotoxin SxIIIA.
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| |
J Am Chem Soc, 130,
14280-14286.
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G.Bulaj,
and
B.M.Olivera
(2008).
Folding of conotoxins: formation of the native disulfide bridges during chemical synthesis and biosynthesis of conus peptides.
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Antioxid Redox Signal, 10,
141-156.
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L.Volpon,
H.Lamthanh,
J.Barbier,
N.Gilles,
J.Molgó,
A.Ménez,
and
J.M.Lancelin
(2004).
NMR solution structures of delta-conotoxin EVIA from Conus ermineus that selectively acts on vertebrate neuronal Na+ channels.
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J Biol Chem, 279,
21356-21366.
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PDB codes:
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N.L.Daly,
J.A.Ekberg,
L.Thomas,
D.J.Adams,
R.J.Lewis,
and
D.J.Craik
(2004).
Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons.
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J Biol Chem, 279,
25774-25782.
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PDB code:
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C.González,
J.L.Neira,
S.Ventura,
S.Bronsoms,
M.Rico,
and
F.X.Avilés
(2003).
Structure and dynamics of the potato carboxypeptidase inhibitor by 1H and 15N NMR.
|
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Proteins, 50,
410-422.
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PDB code:
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M.Price-Carter,
G.Bulaj,
and
D.P.Goldenberg
(2002).
Initial disulfide formation steps in the folding of an omega-conotoxin.
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Biochemistry, 41,
3507-3519.
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D.P.Goldenberg,
R.E.Koehn,
D.E.Gilbert,
and
G.Wagner
(2001).
Solution structure and backbone dynamics of an omega-conotoxin precursor.
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Protein Sci, 10,
538-550.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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