1ag7: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1ag7.gif|left|200px]] | [[Image:1ag7.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1ag7", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_1ag7| PDB=1ag7 | SCENE= }} | |||
}} | |||
'''CONOTOXIN GS, NMR, 20 STRUCTURES''' | '''CONOTOXIN GS, NMR, 20 STRUCTURES''' | ||
| Line 28: | Line 25: | ||
[[Category: Craik, D J.]] | [[Category: Craik, D J.]] | ||
[[Category: Hill, J M.]] | [[Category: Hill, J M.]] | ||
[[Category: | [[Category: Cystine knot motif]] | ||
[[Category: | [[Category: Mu-conotoxin]] | ||
[[Category: | [[Category: Neurotoxin]] | ||
[[Category: | [[Category: Sodium channel blocker]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:13:40 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 10:13, 2 May 2008
CONOTOXIN GS, NMR, 20 STRUCTURES
OverviewOverview
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 StructureAbout this Structure
1AG7 is a Single protein structure of sequence from Conus geographus. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Fri May 2 10:13:40 2008