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2h8s

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Solution structure of alpha-conotoxin Vc1.1

Structural highlights

2h8s is a 1 chain structure with sequence from Conus victoriae. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CA1A_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 1: / Line 1: @@
-{{Seed}}
-[[Image:2h8s.png|left|200px]]
-<!--
+==Solution structure of alpha-conotoxin Vc1.1==
-The line below this paragraph, containing "STRUCTURE_2h8s", creates the "Structure Box" on the page.
+<StructureSection load='2h8s' size='340' side='right'caption='[[2h8s]]' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2h8s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_victoriae Conus victoriae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H8S FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-{{STRUCTURE_2h8s|  PDB=2h8s  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h8s OCA], [https://pdbe.org/2h8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h8s RCSB], [https://www.ebi.ac.uk/pdbsum/2h8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h8s ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CA1A_CONVC CA1A_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 ==
+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.
-===Solution structure of alpha-conotoxin Vc1.1===
+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<ref>PMID:16754662</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_16754662}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 2h8s" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 16754662 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16754662}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Conus victoriae]]
-H8S is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H8S OCA].
+[[Category: Large Structures]]
+[[Category: Adams DJ]]
-==Reference==
+[[Category: Clark RJ]]
-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:[http://www.ncbi.nlm.nih.gov/pubmed/16754662 16754662]
+[[Category: Craik DJ]]
-[[Category: Single protein]]
+[[Category: Fischer H]]
-[[Category: Adams, D J.]]
+[[Category: Nevin ST]]
-[[Category: Clark, R J.]]
-[[Category: Craik, D J.]]
-[[Category: Fischer, H.]]
-[[Category: Nevin, S T.]]
-[[Category: Alpha-conotoxin]]
-[[Category: Alpha-helix]]
-[[Category: Amidated c-terminus]]
-[[Category: Disulfide bond]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:45:18 2008''

2h8s

From Proteopedia

Current revision

Solution structure of alpha-conotoxin Vc1.1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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