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| | ==Solution NMR structure of peptide ImI1 (peak 2)== | | ==Solution NMR structure of peptide ImI1 (peak 2)== |
| - | <StructureSection load='2moa' size='340' side='right'caption='[[2moa]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2moa' size='340' side='right'caption='[[2moa]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2moa]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MOA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2MOA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2moa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_imperialis Conus imperialis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MOA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MOA FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=81S:(4S)-4,5-DISULFANYL-L-NORVALINE'>81S</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4os1|4os1]], [[4os2|4os2]], [[4os4|4os4]], [[4os5|4os5]], [[4os6|4os6]], [[4os7|4os7]], [[1imi|1imi]], [[1im1|1im1]], [[1cnl|1cnl]], [[2c9t|2c9t]], [[1g2g|1g2g]], [[1e74|1e74]], [[2bc7|2bc7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=81S:(4S)-4,5-DISULFANYL-L-NORVALINE'>81S</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PRD_001232:Alpha-conotoxin+ImI+mutant'>PRD_001232</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2moa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2moa OCA], [http://pdbe.org/2moa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2moa RCSB], [http://www.ebi.ac.uk/pdbsum/2moa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2moa ProSAT]</span></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=2moa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2moa OCA], [https://pdbe.org/2moa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2moa RCSB], [https://www.ebi.ac.uk/pdbsum/2moa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2moa ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CA1_CONIM CA1_CONIM]] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.<ref>PMID:8206995</ref> | + | [https://www.uniprot.org/uniprot/CA1_CONIM CA1_CONIM] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.<ref>PMID:8206995</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Conus imperialis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, S]] | + | [[Category: Chen S]] |
| - | [[Category: Heinis, C]] | + | [[Category: Heinis C]] |
| - | [[Category: Bicyclic peptide]]
| + | |
| - | [[Category: Conotoxin]]
| + | |
| - | [[Category: Dithiol amino acid]]
| + | |
| - | [[Category: Macrocycle]]
| + | |
| - | [[Category: Phage display]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
CA1_CONIM Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.[1]
Publication Abstract from PubMed
The disulfide bonds that form between two cysteine residues are important in defining and rigidifying the structures of proteins and peptides. In polypeptides containing multiple cysteine residues, disulfide isomerization can lead to multiple products with different biological activities. Here, we describe the development of a dithiol amino acid (Dtaa) that can form two disulfide bridges at a single amino acid site. Application of Dtaas to a serine protease inhibitor and a nicotinic acetylcholine receptor inhibitor that contain disulfide constraints enhanced their inhibitory activities 40- and 7.6-fold, respectively. X-ray crystallographic and NMR structure analysis show that the peptide ligands containing Dtaas have retained their native tertiary structures. We furthermore show that replacement of two cysteines by Dtaas can avoid the formation of disulfide bond isomers. With these properties, Dtaas are likely to have broad application in the rational design or directed evolution of peptides and proteins with high activity and stability.
Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides.,Chen S, Gopalakrishnan R, Schaer T, Marger F, Hovius R, Bertrand D, Pojer F, Heinis C Nat Chem. 2014 Nov;6(11):1009-16. doi: 10.1038/nchem.2043. Epub 2014 Aug 31. PMID:25343607[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McIntosh JM, Yoshikami D, Mahe E, Nielsen DB, Rivier JE, Gray WR, Olivera BM. A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI. J Biol Chem. 1994 Jun 17;269(24):16733-9. PMID:8206995
- ↑ Chen S, Gopalakrishnan R, Schaer T, Marger F, Hovius R, Bertrand D, Pojer F, Heinis C. Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides. Nat Chem. 2014 Nov;6(11):1009-16. doi: 10.1038/nchem.2043. Epub 2014 Aug 31. PMID:25343607 doi:http://dx.doi.org/10.1038/nchem.2043
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