1xgc
From Proteopedia
(New page: 200px<br /><applet load="1xgc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xgc" /> '''ALPHA CONOTOXIN GI: 2-3;7-13 DISULFIDE BOND ...) |
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'''ALPHA CONOTOXIN GI: 2-3;7-13 DISULFIDE BOND ISOMER, NMR, 25 STRUCTURES'''<br /> | '''ALPHA CONOTOXIN GI: 2-3;7-13 DISULFIDE BOND ISOMER, NMR, 25 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three possible disulfide bonded isomers of alpha-conotoxin GI have | + | The three possible disulfide bonded isomers of alpha-conotoxin GI have been selectively synthesised and their structures determined by 1H NMR spectroscopy. alpha-Conotoxin GI derives from the venom of Conus geographus and is a useful neuropharmacological tool as it selectively binds to the nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel involved in nerve signal transmission. The peptide has the sequence ECCNPACGRHYSC-NH2, and the three disulfide bonded isomers are referred to as GI(2-7;3-13), GI(2-13;3-7) and GI(2-3;7-13). The NMR structure for the native isomer GI(2-7;3-13) is of excellent quality, with a backbone pairwise RMSD of 0.16 A for a family of 35 structures, and comprises primarily a distorted 310 helix between residues 5 to 11. The two non-native isomers exhibit multiple conformers in solution, with the major populated forms being different in structure both from each other and from the native form. Structure-activity relationships for the native GI(2-7;3-13) as well as the role of the disulfide bonds on folding and stability of the three isomers are examined. It is concluded that the disulfide bonds in alpha-conotoxin GI play a crucial part in determining both the structure and stability of the peptide. A trend for increased conformational heterogeneity was observed in the order of GI(2-7;3-13)<GI(2-13;3-7)<GI(2-3;7-13). It was found that the peptide bond joining Cys2 to Cys3 in GI(2-3;7-13) is predominantly trans, rather than cis as theoretically predicted. These structural data are used to interpret the varying nAChR binding of the non-native forms.A model for the binding of native GI(2-7;3-13) to the mammalian nAChR is proposed, with an alpha-subunit binding face made up of Cys2, Asn4, Pro5, Ala6 and Cys7 and a selectivity face, comprised of Arg9 and His10. These two faces orient the molecule between the alpha and delta subunits of the receptor. The structure of the CCNPAC sequence of the native GI(2-7;3-13) is compared to the structure of the identical sequence from the toxic domain of heat-stable enterotoxins, which forms part of the receptor binding region of the enterotoxins, but which has a different disulfide connectivity. |
==About this Structure== | ==About this Structure== | ||
| - | 1XGC 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:// | + | 1XGC 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=1XGC OCA]. |
==Reference== | ==Reference== | ||
Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: a model for the role of disulfide bonds in structural stability., Gehrmann J, Alewood PF, Craik DJ, J Mol Biol. 1998 May 1;278(2):401-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9571060 9571060] | Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: a model for the role of disulfide bonds in structural stability., Gehrmann J, Alewood PF, Craik DJ, J Mol Biol. 1998 May 1;278(2):401-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9571060 9571060] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Alewood, P | + | [[Category: Alewood, P F.]] |
| - | [[Category: Craik, D | + | [[Category: Craik, D J.]] |
[[Category: Gehrmann, J.]] | [[Category: Gehrmann, J.]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
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[[Category: nicotinic acetylcholine recepto disulfide bond isomers]] | [[Category: nicotinic acetylcholine recepto disulfide bond isomers]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:29 2008'' |
Revision as of 13:54, 21 February 2008
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ALPHA CONOTOXIN GI: 2-3;7-13 DISULFIDE BOND ISOMER, NMR, 25 STRUCTURES
Overview
The three possible disulfide bonded isomers of alpha-conotoxin GI have been selectively synthesised and their structures determined by 1H NMR spectroscopy. alpha-Conotoxin GI derives from the venom of Conus geographus and is a useful neuropharmacological tool as it selectively binds to the nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel involved in nerve signal transmission. The peptide has the sequence ECCNPACGRHYSC-NH2, and the three disulfide bonded isomers are referred to as GI(2-7;3-13), GI(2-13;3-7) and GI(2-3;7-13). The NMR structure for the native isomer GI(2-7;3-13) is of excellent quality, with a backbone pairwise RMSD of 0.16 A for a family of 35 structures, and comprises primarily a distorted 310 helix between residues 5 to 11. The two non-native isomers exhibit multiple conformers in solution, with the major populated forms being different in structure both from each other and from the native form. Structure-activity relationships for the native GI(2-7;3-13) as well as the role of the disulfide bonds on folding and stability of the three isomers are examined. It is concluded that the disulfide bonds in alpha-conotoxin GI play a crucial part in determining both the structure and stability of the peptide. A trend for increased conformational heterogeneity was observed in the order of GI(2-7;3-13)<GI(2-13;3-7)<GI(2-3;7-13). It was found that the peptide bond joining Cys2 to Cys3 in GI(2-3;7-13) is predominantly trans, rather than cis as theoretically predicted. These structural data are used to interpret the varying nAChR binding of the non-native forms.A model for the binding of native GI(2-7;3-13) to the mammalian nAChR is proposed, with an alpha-subunit binding face made up of Cys2, Asn4, Pro5, Ala6 and Cys7 and a selectivity face, comprised of Arg9 and His10. These two faces orient the molecule between the alpha and delta subunits of the receptor. The structure of the CCNPAC sequence of the native GI(2-7;3-13) is compared to the structure of the identical sequence from the toxic domain of heat-stable enterotoxins, which forms part of the receptor binding region of the enterotoxins, but which has a different disulfide connectivity.
About this Structure
1XGC is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: a model for the role of disulfide bonds in structural stability., Gehrmann J, Alewood PF, Craik DJ, J Mol Biol. 1998 May 1;278(2):401-15. PMID:9571060
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