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| {{STRUCTURE_1mtq| PDB=1mtq | SCENE= }} | | {{STRUCTURE_1mtq| PDB=1mtq | SCENE= }} |
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| '''THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY'''
| | ===THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY=== |
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| ==Overview==
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| Using assay-directed fractionation of Conus geographus crude venom, we isolated alpha-conotoxin GID, which acts selectively at neuronal nicotinic acetylcholine receptors (nAChRs). Unlike other neuronally selective alpha-conotoxins, alpha-GID has a four amino acid N-terminal tail, gamma-carboxyglutamate (Gla), and hydroxyproline (O) residues, and lacks an amidated C terminus. GID inhibits alpha 7 and alpha 3 beta 2 nAChRs with IC(50) values of 5 and 3 nm, respectively and is at least 1000-fold less potent at the alpha 1 beta 1 gamma delta, alpha 3 beta 4, and alpha 4 beta 4 combinations. GID also potently inhibits the alpha 4 beta 2 subtype (IC(50) of 150 nm). Deletion of the N-terminal sequence (GID Delta 1-4) significantly decreased activity at the alpha 4 beta 2 nAChR but hardly affected potency at alpha 3 beta 2 and alpha 7 nAChRs, despite enhancing the off-rates at these receptors. In contrast, Arg(12) contributed to alpha 4 beta 2 and alpha 7 activity but not to alpha 3 beta 2 activity. The three-dimensional structure of GID is well defined over residues 4-19 with a similar motif to other alpha-conotoxins. However, despite its influence on activity, the tail appears to be disordered in solution. Comparison of GID with other alpha 4/7-conotoxins which possess an NN(P/O) motif in loop II, revealed a correlation between increasing length of the aliphatic side-chain in position 10 (equivalent to 13 in GID) and greater alpha 7 versus alpha 3 beta 2 selectivity.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12419800}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12419800 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12419800}} |
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| ==About this Structure== | | ==About this Structure== |
| Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MTQ OCA]. | | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MTQ OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Nicke, A.]] | | [[Category: Nicke, A.]] |
| [[Category: Alpha-helix]] | | [[Category: Alpha-helix]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:42:19 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 20:02:17 2008'' |
