2moa

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== 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MOA FirstGlance]. <br>
<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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MOA FirstGlance]. <br>
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</td></tr><tr><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>
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</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>
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<tr><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>
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<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>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2moa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2moa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2moa RCSB], [http://www.ebi.ac.uk/pdbsum/2moa PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2moa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2moa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2moa RCSB], [http://www.ebi.ac.uk/pdbsum/2moa PDBsum]</span></td></tr>
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<table>
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</table>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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alpha-Conotoxin ImI derives from the venom of Conus imperialis and is the first and only small-peptide ligand that selectively binds to the neuronal alpha7 homopentameric subtype of the nicotinic acetylcholine receptor (nAChR). This receptor subtype is a possible drug target for several neurological disorders. The cysteines are connected in the pairs Cys2-Cys8 and Cys3-Cys12. To date it is the only alpha-conotoxin with a 4/3 residue spacing between the cysteines. The structure of ImI has been determined by 1H NMR spectroscopy in aqueous solution. The NMR structure is of high quality, with a backbone pairwise rmsd of 0.34 A for a family of 19 structures, and comprises primarily a series of nested beta turns. Addition of organic solvent does not perturb the solution structure. The first eight residues of ImI are identical to the larger, but related, conotoxin EpI and adopt a similar structure, despite a truncated second loop. Residues important for binding of ImI to the alpha7 nAChR are all clustered on one face of the molecule. Once further binding data for EpI and ImI are available, the ImI structure will allow for design of novel alpha7 nAChR-specific agonists and antagonists with a wide range of potential pharmaceutical applications.
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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.
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Solution structure of alpha-conotoxin ImI by 1H nuclear magnetic resonance.,Gehrmann J, Daly NL, Alewood PF, Craik DJ J Med Chem. 1999 Jul 1;42(13):2364-72. PMID:10395477<ref>PMID:10395477</ref>
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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<ref>PMID:25343607</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 06:43, 5 November 2014

Solution NMR structure of peptide ImI1 (peak 2)

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