1mtq
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1mtq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mtq" /> '''THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPH...)
Next diff →
Revision as of 19:34, 20 November 2007
|
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
1MTQ is a Protein complex structure of sequences from [1]. 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 Tue Nov 20 21:41:28 2007
