2mdq

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(New page: '''Unreleased structure''' The entry 2mdq is ON HOLD Authors: Schroeder, C.I. Description: A Novel 4/7-Conotoxin LvIA from Conus lividus that Selectively Blocks 3 2 vs. 6/3 2 3 Nicotin...)
Current revision (05:21, 17 October 2024) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 2mdq is ON HOLD
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==A Novel 4/7-Conotoxin LvIA from Conus lividus that Selectively Blocks 3 2 vs. 6/3 2 3 Nicotinic Acetylcholine Receptors==
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<StructureSection load='2mdq' size='340' side='right'caption='[[2mdq]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2mdq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_lividus Conus lividus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MDQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MDQ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mdq OCA], [https://pdbe.org/2mdq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mdq RCSB], [https://www.ebi.ac.uk/pdbsum/2mdq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mdq ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CA1A_CONLI CA1A_CONLI] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks alpha-3-beta-2/CHRNA3-CHRNB2 nAChR with high selectivity (IC(50)=8.67 nM (on rat) and 17.5 (on human)) (PubMed:24398291). Has also weaker activity on alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) (IC(50)=108 nM (on rat)), alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) (IC(50)=121 nM (on rat)), alpha-3-beta-4 (CHRNA3-CHRNB4) (IC(50)=148 nM (on rat)), and alpha-7/CHRNA7 nAChRs (IC(50)=3000 nM (on rat)) (PubMed:24398291). When tested on mouse with hot-plate tests, this toxin significantly increases the base pain threshold and shows analgesic effects (PubMed:26742048).<ref>PMID:24398291</ref> <ref>PMID:26742048</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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This study was performed to discover and characterize the first potent alpha3beta2-subtype-selective nicotinic acetylcholine receptor (nAChR) ligand. A novel alpha4/7-conotoxin, alpha-CTxLvIA, was cloned from Conus lividus. Its pharmacological profile at Xenopus laevis oocyte-expressed rat nAChR subtypes was determined by 2-electrode voltage-clamp electrophysiology, and its 3-dimensional (3D) structure was determined by NMR spectroscopy. alpha-CTx LvIA is a 16-aa C-terminally-amidated peptide with 2-disulfide bridges. Using rat subunits expressed in Xenopus oocytes, we found the highest affinity of alpha-CTxLvIA was for alpha3beta2 nAChRs (IC50 8.7 nM), where blockade was reversible within 2 min. IC50 values were &gt;100 nM at alpha6/alpha3beta2beta3, alpha6/alpha3beta4, and alpha3beta4 nAChRs, and &gt;/=3 muM at all other subtypes tested. alpha3beta2 vs. alpha6beta2 subtype selectivity was confirmed for human-subunit nAChRs with much greater preference (300-fold) for alpha3beta2 over alpha6beta2 nAChRs. This is the first alpha-CTx reported to show high selectivity for human alpha3beta2 vs. alpha6beta2 nAChRs. alpha-CTxLvIA adopts two similarly populated conformations water: one (assumed to be bioactive) is highly structured, whereas the other is mostly random coil in nature. Selectivity differences with the similarly potent, but less selective, alpha3beta2 nAChR antagonist alpha-CTx PeIA probably reside within the three residues, which differ in loop 2, given their otherwise similar 3D structures. alpha4/7-CTx LvIA is a new, potent, selective alpha3beta2 nAChR antagonist, which will enable detailed studies of alpha3beta2 nAChR structure, function, and physiological roles.-Luo, S., Zhangsun, D., Schroeder, C. I., Zhu, X., Hu, Y., Wu, Y., Weltzin, M. M., Eberhard, S., Kaas, Q., Craik, D. J., McIntosh, J. M., Whiteaker, P. A novel alpha4/7-conotoxin LvIA from Conus lividus that selectively blocks alpha3beta2 vs. alpha6/alpha3beta2beta3 nicotinic acetylcholine receptors.
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Authors: Schroeder, C.I.
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A novel alpha4/7-conotoxin LvIA from Conus lividus that selectively blocks alpha3beta2 vs. alpha6/alpha3beta2beta3 nicotinic acetylcholine receptors.,Luo S, Zhangsun D, Schroeder CI, Zhu X, Hu Y, Wu Y, Weltzin MM, Eberhard S, Kaas Q, Craik DJ, McIntosh JM, Whiteaker P FASEB J. 2014 Jan 7. PMID:24398291<ref>PMID:24398291</ref>
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Description: A Novel 4/7-Conotoxin LvIA from Conus lividus that Selectively Blocks 3 2 vs. 6/3 2 3 Nicotinic Acetylcholine Receptors
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2mdq" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Conus lividus]]
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[[Category: Large Structures]]
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[[Category: Schroeder CI]]

Current revision

A Novel 4/7-Conotoxin LvIA from Conus lividus that Selectively Blocks 3 2 vs. 6/3 2 3 Nicotinic Acetylcholine Receptors

PDB ID 2mdq

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