7n25
From Proteopedia
(Difference between revisions)
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<StructureSection load='7n25' size='340' side='right'caption='[[7n25]]' scene=''> | <StructureSection load='7n25' size='340' side='right'caption='[[7n25]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full | + | <table><tr><td colspan='2'>[[7n25]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_episcopatus Conus episcopatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N25 FirstGlance]. <br> |
| - | </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=7n25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n25 OCA], [https://pdbe.org/7n25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n25 RCSB], [https://www.ebi.ac.uk/pdbsum/7n25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n25 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</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=7n25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n25 OCA], [https://pdbe.org/7n25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n25 RCSB], [https://www.ebi.ac.uk/pdbsum/7n25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n25 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CA1A_CONEP CA1A_CONEP] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This peptide blocks mammalian nicotinic acetylcholine receptors composed of alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-3-beta-4/CHRNA3-CHRNB4 subunits.<ref>PMID:9624161</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Conotoxins are peptides found in the venoms of marine cone snails. They are typically highly structured and stable and have potent activities at nicotinic acetylcholine receptors, which make them valuable research tools and promising lead molecules for drug development. Many conotoxins are also highly modified with posttranslational modifications such as proline hydroxylation, glutamic acid gamma-carboxylation, tyrosine sulfation and C-terminal amidation, amongst others. The role of these posttranslational modifications is poorly understood, and it is unclear whether the modifications interact directly with the binding site, alter conotoxin structure, or both. Here we synthesised a set of twelve conotoxin variants bearing posttranslational modifications in the form of native sulfotyrosine and C-terminal amidation and show that these two modifications in combination increase their activity at nicotinic acetylcholine receptors and binding to soluble acetylcholine binding proteins, respectively. We then rationalise how these functional differences between variants might arise from stabilization of the three-dimensional structures and interactions with the binding sites, using high-resolution nuclear magnetic resonance data. This study demonstrates that posttranslational modifications can modulate interactions between a ligand and receptor by a combination of structural and binding alterations. A deeper mechanistic understanding of the role of posttranslational modifications in structure-activity relationships is essential for understanding receptor biology and could help to guide structure-based drug design. | ||
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| + | Posttranslational modifications of alpha-conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding.,Ho TNT, Lee HS, Swaminathan S, Goodwin L, Rai N, Ushay B, Lewis RJ, Rosengren KJ, Conibear AC RSC Med Chem. 2021 Jul 26;12(9):1574-1584. doi: 10.1039/d1md00182e. eCollection, 2021 Sep 23. PMID:34671739<ref>PMID:34671739</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7n25" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Conus episcopatus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Conibear AC]] | [[Category: Conibear AC]] | ||
[[Category: Lee HS]] | [[Category: Lee HS]] | ||
[[Category: Rosengren KJ]] | [[Category: Rosengren KJ]] | ||
Revision as of 11:17, 14 June 2023
NMR structure of EpI-OH
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