1mtq

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(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...)
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'''THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY'''<br />
'''THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY'''<br />
==Overview==
==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.
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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.
==About this Structure==
==About this Structure==
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1MTQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MTQ OCA].
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1MTQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. 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://ispc.weizmann.ac.il//pmbin/getpm?pmid=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://ispc.weizmann.ac.il//pmbin/getpm?pmid=12419800 12419800]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Adams, D.J.]]
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[[Category: Adams, D J.]]
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[[Category: Alewood, P.F.]]
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[[Category: Alewood, P F.]]
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[[Category: Craik, D.J.]]
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[[Category: Craik, D J.]]
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[[Category: Daly, N.L.]]
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[[Category: Daly, N L.]]
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[[Category: Lewis, R.J.]]
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[[Category: Lewis, R J.]]
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[[Category: Loughnan, M.L.]]
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[[Category: Loughnan, M L.]]
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[[Category: Millard, E.L.]]
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[[Category: Millard, E L.]]
[[Category: Nicke, A.]]
[[Category: Nicke, A.]]
[[Category: alpha-helix]]
[[Category: alpha-helix]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:41:28 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:58:55 2008''

Revision as of 11:58, 21 February 2008

Image:1mtq.jpg

1mtq

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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

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