1mtq: Difference between revisions

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[[Image:1mtq.jpg|left|200px]]<br /><applet load="1mtq" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1mtq.jpg|left|200px]]<br /><applet load="1mtq" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1mtq" />

'''THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY'''<br />

==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.

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 [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].

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==

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: Adams, D.J.]]

[[Category: Adams, D J.]]

[[Category: Alewood, P.F.]]

[[Category: Alewood, P F.]]

[[Category: Craik, D.J.]]

[[Category: Craik, D J.]]

[[Category: Daly, N.L.]]

[[Category: Daly, N L.]]

[[Category: Lewis, R.J.]]

[[Category: Lewis, R J.]]

[[Category: Loughnan, M.L.]]

[[Category: Loughnan, M L.]]

[[Category: Millard, E.L.]]

[[Category: Millard, E L.]]

[[Category: Nicke, A.]]

[[Category: alpha-helix]]

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@@ Line 1: / Line 1: @@
-[[Image:1mtq.jpg|left|200px]]<br /><applet load="1mtq" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1mtq.jpg|left|200px]]<br /><applet load="1mtq" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1mtq" />
 '''THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY'''<br />
 ==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.
+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==
-MTQ 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].
+MTQ 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==
 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: Adams, D.J.]]
+[[Category: Adams, D J.]]
-[[Category: Alewood, P.F.]]
+[[Category: Alewood, P F.]]
-[[Category: Craik, D.J.]]
+[[Category: Craik, D J.]]
-[[Category: Daly, N.L.]]
+[[Category: Daly, N L.]]
-[[Category: Lewis, R.J.]]
+[[Category: Lewis, R J.]]
-[[Category: Loughnan, M.L.]]
+[[Category: Loughnan, M L.]]
-[[Category: Millard, E.L.]]
+[[Category: Millard, E L.]]
 [[Category: Nicke, A.]]
 [[Category: alpha-helix]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:41:28 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:58:55 2008''