1mtq
From Proteopedia
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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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==About this Structure== | ==About this Structure== | ||
- | + | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MTQ OCA]. | |
==Reference== | ==Reference== | ||
Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence., Nicke A, Loughnan ML, Millard EL, Alewood PF, Adams DJ, Daly NL, Craik DJ, Lewis RJ, J Biol Chem. 2003 Jan 31;278(5):3137-44. Epub 2002 Nov 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12419800 12419800] | Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence., Nicke A, Loughnan ML, Millard EL, Alewood PF, Adams DJ, Daly NL, Craik DJ, Lewis RJ, J Biol Chem. 2003 Jan 31;278(5):3137-44. Epub 2002 Nov 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12419800 12419800] | ||
- | [[Category: Protein complex]] | ||
[[Category: Adams, D J.]] | [[Category: Adams, D J.]] | ||
[[Category: Alewood, P F.]] | [[Category: Alewood, P F.]] | ||
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[[Category: Millard, E L.]] | [[Category: Millard, E L.]] | ||
[[Category: Nicke, A.]] | [[Category: Nicke, A.]] | ||
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Revision as of 22:42, 2 May 2008
THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY
Overview
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.
About this Structure
Full crystallographic information is available from OCA.
Reference
Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence., Nicke A, Loughnan ML, Millard EL, Alewood PF, Adams DJ, Daly NL, Craik DJ, Lewis RJ, J Biol Chem. 2003 Jan 31;278(5):3137-44. Epub 2002 Nov 4. PMID:12419800 Page seeded by OCA on Sat May 3 01:42:19 2008