|
|
| (12 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:2bc8.gif|left|200px]] | |
| | | | |
| - | {{Structure
| + | ==[Sec2,3,8,12]-ImI== |
| - | |PDB= 2bc8 |SIZE=350|CAPTION= <scene name='initialview01'>2bc8</scene>
| + | <StructureSection load='2bc8' size='340' side='right'caption='[[2bc8]]' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[2bc8]] 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=2BC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BC8 FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | |GENE=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [https://pdbe.org/2bc8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [https://www.ebi.ac.uk/pdbsum/2bc8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bc8 ProSAT]</span></td></tr> |
| - | |DOMAIN=
| + | </table> |
| - | |RELATEDENTRY=[[2bc7|2BC7]]
| + | == Function == |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB]</span>
| + | [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> |
| - | }}
| + | == References == |
| - | | + | <references/> |
| - | '''[Sec2,3,8,12]-ImI'''
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | | + | [[Category: Conus imperialis]] |
| - | ==Overview== | + | [[Category: Large Structures]] |
| - | Disulfide bonds are important structural motifs that play an essential role in maintaining the conformational stability of many bioactive peptides. Of particular importance are the conotoxins, which selectively target a wide range of ion channels that are implicated in numerous disease states. Despite the enormous potential of conotoxins as therapeutics, their multiple disulfide bond frameworks are inherently unstable under reducing conditions. Reduction or scrambling by thiol-containing molecules such as glutathione or serum albumin in intracellular or extracellular environments such as blood plasma can decrease their effectiveness as drugs. To address this issue, we describe a new class of selenoconotoxins where cysteine residues are replaced by selenocysteine to form isosteric and nonreducible diselenide bonds. Three isoforms of alpha-conotoxin ImI were synthesized by t-butoxycarbonyl chemistry with systematic replacement of one ([Sec(2,8)]ImI or [Sec(3,12)]ImI), or both ([Sec(2,3,8,12)]ImI) disulfide bonds with a diselenide bond. Each analogue demonstrated remarkable stability to reduction or scrambling under a range of chemical and biological reducing conditions. Three-dimensional structural characterization by NMR and CD spectroscopy indicates conformational preferences that are very similar to those of native ImI, suggesting fully isomorphic structures. Additionally, full bioactivity was retained at the alpha7 nicotinic acetylcholine receptor, with each selenoanalogue exhibiting a dose-response curve that overlaps with wild-type ImI, thus further supporting an isomorphic structure. These results demonstrate that selenoconotoxins can be used as highly stable scaffolds for the design of new drugs.
| + | [[Category: Armishaw CJ]] |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 2BC8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BC8 OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | Alpha-selenoconotoxins, a new class of potent alpha7 neuronal nicotinic receptor antagonists., Armishaw CJ, Daly NL, Nevin ST, Adams DJ, Craik DJ, Alewood PF, J Biol Chem. 2006 May 19;281(20):14136-43. Epub 2006 Feb 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16500898 16500898]
| + | |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Armishaw, C J.]]
| + | |
| - | [[Category: conotoxin]] | + | |
| - | [[Category: diselenide bond]] | + | |
| - | [[Category: disulfide bond]] | + | |
| - | [[Category: helix]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:04:13 2008''
| + | |
