1ag7
From Proteopedia
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CONOTOXIN GS, NMR, 20 STRUCTURES
Overview
BACKGROUND: The venoms of Conus snails contain small, disulfide-rich, inhibitors of voltage-dependent sodium channels. Conotoxin GS is a, 34-residue polypeptide isolated from Conus geographus that interacts with, the extracellular entrance of skeletal muscle sodium channels to prevent, sodium ion conduction. Although conotoxin GS binds competitively with mu, conotoxin GIIIA to the sodium channel surface, the two toxin types have, little sequence identity with one another, and conotoxin GS has a, four-loop structural framework rather than the characteristic three-loop, mu-conotoxin framework. The structural study of conotoxin GS will form the, basis for establishing a structure-activity relationship and understanding, its interaction with the pore region of sodium channels. RESULTS: The, three-dimensional structure of conotoxin GS was determined using, two-dimensional NMR spectroscopy. The protein exhibits a compact fold, incorporating a beta hairpin and several turns. An unusual feature of, conotoxin GS is the exceptionally high proportion (100%) of cis-imide bond, geometry for the three proline or hydroxyproline residues. The structure, of conotoxin GS bears little resemblance to the three-loop mu conotoxins, consistent with the low sequence identity between the two toxin types and, their different structural framework. However, the tertiary structure and, cystine-knot motif formed by the three disulfide bonds is similar to that, present in several other polypeptide ion channel inhibitors. CONCLUSIONS:, This is the first three-dimensional structure of a 'four-loop' sodium, channel inhibitor, and it represents a valuable new structural probe for, the pore region of voltage-dependent sodium channels. The distribution of, amino acid sidechains in the structure creates several polar and charged, patches, and comparison with the mu conotoxins provides a basis for, determining the binding surface of the conotoxin GS polypeptide.
About this Structure
1AG7 is a Single protein structure of sequence from Conus geographus. Full crystallographic information is available from OCA.
Reference
Solution structure of the sodium channel antagonist conotoxin GS: a new molecular caliper for probing sodium channel geometry., Hill JM, Alewood PF, Craik DJ, Structure. 1997 Apr 15;5(4):571-83. PMID:9115446
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