2h8s: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /><applet load="2h8s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h8s" /> '''Solution structure of alpha-conotoxin Vc1.1'... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2h8s.gif|left|200px]]<br /><applet load="2h8s" size=" | [[Image:2h8s.gif|left|200px]]<br /><applet load="2h8s" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2h8s" /> | caption="2h8s" /> | ||
'''Solution structure of alpha-conotoxin Vc1.1'''<br /> | '''Solution structure of alpha-conotoxin Vc1.1'''<br /> | ||
==Overview== | ==Overview== | ||
The alpha-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in | 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. | ||
==About this Structure== | ==About this Structure== | ||
2H8S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2H8S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H8S OCA]. | ||
==Reference== | ==Reference== | ||
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=16754662 16754662] | 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://ispc.weizmann.ac.il//pmbin/getpm?pmid=16754662 16754662] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Adams, D | [[Category: Adams, D J.]] | ||
[[Category: Clark, R | [[Category: Clark, R J.]] | ||
[[Category: Craik, D | [[Category: Craik, D J.]] | ||
[[Category: Fischer, H.]] | [[Category: Fischer, H.]] | ||
[[Category: Nevin, S | [[Category: Nevin, S T.]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
[[Category: alpha-conotoxin]] | [[Category: alpha-conotoxin]] | ||
| Line 23: | Line 23: | ||
[[Category: disulfide bonds]] | [[Category: disulfide bonds]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:39:21 2008'' | ||
