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==Dimeric alpha-cobratoxin X-ray structure: Localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors==
==Dimeric alpha-cobratoxin X-ray structure: Localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors==
<StructureSection load='4aea' size='340' side='right' caption='[[4aea]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
<StructureSection load='4aea' size='340' side='right'caption='[[4aea]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4aea]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AEA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AEA FirstGlance]. <br>
<table><tr><td colspan='2'>[[4aea]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AEA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lxh|1lxh]], [[1lxg|1lxg]], [[1ctx|1ctx]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></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=4aea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aea OCA], [http://pdbe.org/4aea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4aea RCSB], [http://www.ebi.ac.uk/pdbsum/4aea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4aea 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=4aea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aea OCA], [https://pdbe.org/4aea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aea RCSB], [https://www.ebi.ac.uk/pdbsum/4aea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aea ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/NXL1_NAJKA NXL1_NAJKA]] The monomeric form binds with high affinity to muscular, Torpedo (muscle-type), and neuronal alpha-7 nicotinic acetylcholine receptors (nAChR). Has no effect on alpha-3/beta-2 nAChR. Causes paralysis by preventing acetylcholine binding to the nAChR. Does not show any blockade of the nicotine-evoked release of dopamine and does not affect ACh release. In mice lung cancer, causes reduction of tumor growth.<ref>PMID:18381281</ref> <ref>PMID:6771288</ref> <ref>PMID:6553056</ref> <ref>PMID:2086254</ref> <ref>PMID:9053737</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref> <ref>PMID:10574958</ref> <ref>PMID:18067132</ref>  The homodimeric form binds with low affinity to Torpedo (muscle-type) and alpha-7 nAChRs, whereas it acquires the capacity to block alpha-3/beta-2 nAChRs.<ref>PMID:18381281</ref> <ref>PMID:6771288</ref> <ref>PMID:6553056</ref> <ref>PMID:2086254</ref> <ref>PMID:9053737</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref> <ref>PMID:10574958</ref> <ref>PMID:18067132</ref>
[https://www.uniprot.org/uniprot/3L21_NAJKA 3L21_NAJKA] Monomer: binds with high affinity to muscular (alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND) nAChR (tested on Torpedo californica, Kd=0.2-4.5 nM) and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (Kd=13-105 nM) (PubMed:18381281, PubMed:22223648, PubMed:9305882). Also inhibits GABA(A) channels (PubMed:26221036). Heteropentamer targets studied are composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits (IC(50)=236 nM), alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits (IC(50)=469 nM), alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits (IC(50)=485 nM), alpha-5-beta-3-gamma-2 (GABRA5-GABRB3-GABRG2) subunits (IC(50)=635 nM), and alpha-2-beta-3-gamma-2 (GABRA2-GABRB3-GABRG2) subunits (IC(50)=1099 nM) (activated by 10 uM GABA) (PubMed:26221036).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref> <ref>PMID:26221036</ref> <ref>PMID:30025921</ref>   Homodimer: binds with high affinity (but lower than the monomeric form) to muscular (IC(50)=9.7 nM) and with low affinity to neuronal alpha-7/CHRNA7 nAChRs (IC(50)=1370 nM) (PubMed:22223648). However, it acquires (compared to the monomeric form) the capacity to block alpha-3/beta-2 (CHRNA3/CHRNB2) nAChRs (PubMed:18381281).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref>   Heterodimer with cytotoxin 3 (AC P01446): is slightly more active than the homodimer in inhibiting alpha-7/CHRNA7 nAChR and is considerably more active in blocking the alpha-3-beta-2/CHRNA3-CHRNB2 nAChR.<ref>PMID:22223648</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: Large Structures]]
[[Category: Naja kaouthia]]
[[Category: Naja kaouthia]]
[[Category: Andreeva, T V]]
[[Category: Andreeva TV]]
[[Category: Bertrand, D]]
[[Category: Bertrand D]]
[[Category: Filkin, S Y]]
[[Category: Filkin SY]]
[[Category: Kasheverov, I E]]
[[Category: Kasheverov IE]]
[[Category: Osipov, A V]]
[[Category: Osipov AV]]
[[Category: Rucktooa, P]]
[[Category: Rucktooa P]]
[[Category: Sixma, T K]]
[[Category: Sixma TK]]
[[Category: Starkov, V G]]
[[Category: Starkov VG]]
[[Category: Tsetlin, V I]]
[[Category: Tsetlin VI]]
[[Category: Utkin, Y N]]
[[Category: Utkin YN]]
[[Category: Nicotinic acetylcholine receptor]]
[[Category: Three-finger toxin]]
[[Category: Toxin]]
Retrieved from "https://proteopedia.org/4aea"