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2h8s

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Revision as of 02:50, 25 December 2014

Solution structure of alpha-conotoxin Vc1.1

Structural highlights

2h8s is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[CXA1A_CONVC] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide (produced without hydroxyproline, nor 4-carboxyglutamate) is a neuronal nAChR antagonist that acts as a powerful analgesic. It blocks nAChRs composed of alpha-3 or -5/beta-2 (IC(50)=7.2 uM), alpha-3/beta-2 (IC(50)=7.3 uM), alpha-3/beta-4 (IC(50)=4.2 uM), alpha-3 or -5/beta-4 (IC(50)<30 uM), alpha-4/beta-2 (IC(50)<30 uM), alpha-4/beta-4 (IC(50)<30 uM) and alpha/beta/gamma/delta (IC(50)<30 uM) subunits.^[1] ^[2]

Publication Abstract from PubMed

The alpha-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in development as a treatment for neuropathic pain. This study describes the synthesis, determination of the disulfide connectivity, and the determination of the three-dimensional structure of Vc1.1 using NMR spectroscopy. Vc1.1 was shown to inhibit nicotine-evoked membrane currents in isolated bovine chromaffin cells in a concentration-dependent manner and preferentially targets peripheral nicotinic acetylcholine receptor (nAChR) subtypes over central subtypes. Specifically, Vc1.1 is selective for alpha3-containing nAChR subtypes. The three-dimensional structure of Vc1.1 comprises a small alpha-helix spanning residues Pro6 to Asp11 and is braced by the I-III, II-IV disulfide connectivity seen in other alpha-conotoxins. A comparison of the structure of Vc1.1 with other alpha-conotoxins, taken together with nAChR selectivity data, suggests that the conserved proline at position 6 is important for binding, whereas a number of residues in the C-terminal portion of the peptide contribute toward the selectivity. The structure reported here should open new opportunities for further development of Vc1.1 or analogues as analgesic agents.

The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1.,Clark RJ, Fischer H, Nevin ST, Adams DJ, Craik DJ J Biol Chem. 2006 Aug 11;281(32):23254-63. Epub 2006 Jun 5. PMID:16754662^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sandall DW, Satkunanathan N, Keays DA, Polidano MA, Liping X, Pham V, Down JG, Khalil Z, Livett BG, Gayler KR. A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry. 2003 Jun 10;42(22):6904-11. PMID:12779345 doi:http://dx.doi.org/10.1021/bi034043e
↑ Lang PM, Burgstahler R, Haberberger RV, Sippel W, Grafe P. A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves. Neuroreport. 2005 Apr 4;16(5):479-83. PMID:15770155
↑ Clark RJ, Fischer H, Nevin ST, Adams DJ, Craik DJ. The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1. J Biol Chem. 2006 Aug 11;281(32):23254-63. Epub 2006 Jun 5. PMID:16754662 doi:M604550200

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2h8s"

@@ Line 6: / Line 6: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h8s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2h8s RCSB], [http://www.ebi.ac.uk/pdbsum/2h8s PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/CXA1A_CONVC CXA1A_CONVC]] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide (produced without hydroxyproline, nor 4-carboxyglutamate) is a neuronal nAChR antagonist that acts as a powerful analgesic. It blocks nAChRs composed of alpha-3 or -5/beta-2 (IC(50)=7.2 uM), alpha-3/beta-2 (IC(50)=7.3 uM), alpha-3/beta-4 (IC(50)=4.2 uM), alpha-3 or -5/beta-4 (IC(50)<30 uM), alpha-4/beta-2 (IC(50)<30 uM), alpha-4/beta-4 (IC(50)<30 uM) and alpha/beta/gamma/delta (IC(50)<30 uM) subunits.<ref>PMID:12779345</ref> <ref>PMID:15770155</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2h8s

From Proteopedia

Revision as of 02:50, 25 December 2014

Solution structure of alpha-conotoxin Vc1.1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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