View source for 1mtq


==THREE-DIMENSIONAL SOLUTION STRUCTURE OF ALPHA-CONOTOXIN GID BY NMR SPECTROSCOPY==
<StructureSection load='1mtq' size='340' side='right'caption='[[1mtq]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mtq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MTQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mtq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mtq OCA], [https://pdbe.org/1mtq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mtq RCSB], [https://www.ebi.ac.uk/pdbsum/1mtq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mtq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CA1D_CONGE CA1D_CONGE] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin reversibly blocks alpha-3-beta-2 (IC(50)=3.1-5.1 nM), alpha-7 (IC(50)=4.5-5.1 nM), and alpha-4-beta-2 (IC(50)=128.6-390 nM) nAChRs.<ref>PMID:12419800</ref> <ref>PMID:15929983</ref> <ref>PMID:19098004</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:12419800</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1mtq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Adams DJ]]
[[Category: Alewood PF]]
[[Category: Craik DJ]]
[[Category: Daly NL]]
[[Category: Lewis RJ]]
[[Category: Loughnan ML]]
[[Category: Millard EL]]
[[Category: Nicke A]]