2bc8 - Revision history

OCA at 06:37, 1 May 2024

2024-05-01T06:37:51Z

← Older revision		Revision as of 06:37, 1 May 2024
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	== Function ==		== Function ==
	[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>		[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;">~~
	~~== Publication Abstract from PubMed ==~~
	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.

	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:16500898<ref>PMID:16500898</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 2bc8" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:34, 30 August 2023

2023-08-30T13:34:50Z

← Older revision		Revision as of 13:34, 30 August 2023
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	==[Sec2,3,8,12]-ImI==		==[Sec2,3,8,12]-ImI==
	<StructureSection load='2bc8' size='340' side='right'caption='[[2bc8~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>		<StructureSection load='2bc8' size='340' side='right'caption='[[2bc8]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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>		<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>
	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style~~=~~'overflow: auto; max-height: 3em;'>[[2bc7\|2bc7]]</div~~></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='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>		<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>
	</table>		</table>
	== Function ==		== Function ==
	[[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>		[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: Armishaw~~, C J]]~~		[[Category: Armishaw CJ]]
	~~[[Category: Conotoxin]]~~
	~~[[Category: Diselenide bond]]~~
	~~[[Category: Disulfide bond]]~~
	~~[[Category: Helix]]~~
	~~[[Category: Toxin~~]]

OCA at 13:07, 24 November 2021

2021-11-24T13:07:53Z

← Older revision		Revision as of 13:07, 24 November 2021
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	<StructureSection load='2bc8' size='340' side='right'caption='[[2bc8]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2bc8' size='340' side='right'caption='[[2bc8]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bc7\|2bc7]]</div></td></tr>
	<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [~~http~~://pdbe.org/2bc8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2bc8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2bc8 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=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>
	</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 ==

OCA at 08:01, 19 February 2020

2020-02-19T08:01:19Z

← Older revision		Revision as of 08:01, 19 February 2020
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	==[Sec2,3,8,12]-ImI==		==[Sec2,3,8,12]-ImI==
	<StructureSection load='2bc8' size='340' side='right' caption='[[2bc8]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2bc8' size='340' side='right'caption='[[2bc8]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Armishaw, C J]]		[[Category: Armishaw, C J]]
	[[Category: Conotoxin]]		[[Category: Conotoxin]]

OCA at 06:23, 16 May 2018

2018-05-16T06:23:57Z

← Older revision		Revision as of 06:23, 16 May 2018
Line 1:		Line 1:

	==[Sec2,3,8,12]-ImI==		==[Sec2,3,8,12]-ImI==
	<StructureSection load='2bc8' size='340' side='right' caption='[[2bc8]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2bc8' size='340' side='right' caption='[[2bc8]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>
	<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://pdbe.org/2bc8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>		<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://pdbe.org/2bc8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bc8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 13:22, 10 September 2015

2015-09-10T13:22:52Z

← Older revision		Revision as of 13:22, 10 September 2015
Line 4:		Line 4:
	<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>
	<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>		<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://pdbe.org/2bc8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 2bc8" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 00:38, 25 December 2014

2014-12-25T00:38:11Z

← Older revision		Revision as of 00:38, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>
	<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>		<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>
	<table>		</table>
			== 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>
	<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: Armishaw, C J.]]		[[Category: Armishaw, C J]]
	[[Category: Conotoxin]]		[[Category: Conotoxin]]
	[[Category: Diselenide bond]]		[[Category: Diselenide bond]]

OCA at 02:52, 7 August 2014

2014-08-07T02:52:26Z

← Older revision		Revision as of 02:52, 7 August 2014
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	~~{{STRUCTURE_2bc8~~\| ~~PDB~~=2bc8 \| ~~SCENE~~= }}		==[Sec2,3,8,12]-ImI==
	===[~~Sec2~~,3,8,12]-ImI~~===~~		<StructureSection load='2bc8' size='340' side='right' caption='[[2bc8]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	~~{{ABSTRACT_PUBMED_16500898}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2bc8]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BC8 FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2bc7\|2bc7]]</td></tr>
			<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=2bc8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bc8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2bc8 RCSB], [http://www.ebi.ac.uk/pdbsum/2bc8 PDBsum]</span></td></tr>
			<table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			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.

	~~==Function==~~		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:16500898<ref>PMID:16500898</ref>
	~~[[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>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[2bc8]] is~~ a ~~1 chain structure. Full experimental information is available from [http://oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=2BC8 OCA].~~		</div>
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:016500898</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Armishaw, C J.]]		[[Category: Armishaw, C J.]]
	[[Category: Conotoxin]]		[[Category: Conotoxin]]

OCA at 07:43, 30 June 2013

2013-06-30T07:43:30Z

← Older revision		Revision as of 07:43, 30 June 2013
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	~~[[Image:2bc8.png\|left\|200px]]~~

	{{STRUCTURE_2bc8\| PDB=2bc8 \| SCENE= }}		{{STRUCTURE_2bc8\| PDB=2bc8 \| SCENE= }}

	===[Sec2,3,8,12]-ImI===		===[Sec2,3,8,12]-ImI===
			{{ABSTRACT_PUBMED_16500898}}

	~~{{ABSTRACT_PUBMED_16500898}}~~		==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>

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
	<ref group="xtra">PMID:016500898</ref><references group="xtra"/>		<ref group="xtra">PMID:016500898</ref><references group="xtra"/><references/>
	[[Category: Armishaw, C J.]]		[[Category: Armishaw, C J.]]
	[[Category: Conotoxin]]		[[Category: Conotoxin]]

OCA: Protected "2bc8" [edit=sysop:move=sysop]

2012-08-14T15:13:51Z

Protected "2bc8" [edit=sysop:move=sysop]

← Older revision	Revision as of 15:13, 14 August 2012
(No difference)