1abt

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[[Image:1abt.png|left|200px]]
 
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==NMR SOLUTION STRUCTURE OF AN ALPHA-BUNGAROTOXIN(SLASH)NICOTINIC RECEPTOR PEPTIDE COMPLEX==
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The line below this paragraph, containing "STRUCTURE_1abt", creates the "Structure Box" on the page.
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<StructureSection load='1abt' size='340' side='right'caption='[[1abt]]' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1abt]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ABT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ABT 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, 4 models</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=1abt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1abt OCA], [https://pdbe.org/1abt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1abt RCSB], [https://www.ebi.ac.uk/pdbsum/1abt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1abt ProSAT]</span></td></tr>
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{{STRUCTURE_1abt| PDB=1abt | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/3L21A_BUNMU 3L21A_BUNMU] Binds with high affinity to muscular (tested on Torpedo marmorata, Kd=0.4 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=0.95 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). It also shows an activity on GABA(A) receptors (PubMed:16549768, PubMed:25634239). It antagonises GABA-activated currents with high potency when tested on primary hippocampal neurons (PubMed:25634239). It inhibits recombinantly expressed GABA(A) receptors composed of alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits with high potency (62.3% inhibition at 20 uM of toxin) (PubMed:25634239). It also shows a weaker inhibition on GABA(A) receptors composed of alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits, alpha-4-beta-2-gamma-2 (GABRA4-GABRB2-GABRG2) subunits, and alpha-5-beta-2-gamma-2 (GABRA5-GABRB2-GABRG2) subunits (PubMed:25634239). A very weak inhibition is also observed on GABA(A) receptor composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) (PubMed:26221036). It has also been shown to bind and inhibit recombinant GABA(A) receptor beta-3/GABRB3 subunit (Kd=about 50 nM) (PubMed:16549768). In addition, it blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM) (PubMed:9840221).<ref>PMID:16549768</ref> <ref>PMID:25634239</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ab/1abt_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1abt ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We report the two-dimensional nuclear magnetic resonance (NMR) characterization of the stoichiometric complex formed between the snake venom-derived long alpha-neurotoxin, alpha-bungarotoxin (BGTX), and a synthetic dodecapeptide (alpha 185-196) corresponding to a functionally important region on the alpha-subunit of the nicotinic acetylcholine receptor (nAChR) obtained from Torpedo californica electric organ tissue. BGTX has been widely used as the classic nicotinic competitive antagonist for the skeletal muscle type of nAChR which is found in the avian, amphibian, and mammalian neuromuscular junction. The receptor dodecapeptide (alpha 185-196) binds BGTX with micromolar affinity and has been shown to represent the major determinant of BGTX binding to the isolated alpha-subunit. Previous studies involving covalent modification of the native nAChR from Torpedo membranes with a variety of affinity reagents indicate that several residues contained within the dodecapeptide sequence (namely, Tyr-190, Cys-192, and Cys-193) apparently contribute directly to the formation of the cholinergic ligand binding site. The NMR-derived solution structure of the BGTX/receptor peptide complex defines a relatively extended conformation for a major segment of the "bound" dodecapeptide. These structural studies also reveal a previously unpredicted receptor binding cleft within BGTX and suggest that BGTX undergoes a conformational change upon peptide binding. If, as we hypothesize, the identified intermolecular contacts in the BGTX/receptor peptide complex describe a portion of the contact zone between BGTX and native receptor, then the structural data would suggest that alpha-subunit residues 186-190 are on the extracellular surface of the receptor.
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===NMR SOLUTION STRUCTURE OF AN ALPHA-BUNGAROTOXIN(SLASH)NICOTINIC RECEPTOR PEPTIDE COMPLEX===
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NMR solution structure of an alpha-bungarotoxin/nicotinic receptor peptide complex.,Basus VJ, Song G, Hawrot E Biochemistry. 1993 Nov 23;32(46):12290-8. PMID:8241115<ref>PMID:8241115</ref>
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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 class="pdbe-citations 1abt" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 8241115 is the PubMed ID number.
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{{ABSTRACT_PUBMED_8241115}}
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==About this Structure==
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[[1abt]] is a 2 chain structure of [[Bungarotoxin]]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ABT OCA].
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==See Also==
==See Also==
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*[[Bungarotoxin]]
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*[[Bungarotoxin 3D structures|Bungarotoxin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:8241115</ref><references group="xtra"/>
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__TOC__
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[[Category: Basus, V J.]]
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</StructureSection>
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[[Category: Hawrot, E.]]
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[[Category: Large Structures]]
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[[Category: Song, G.]]
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[[Category: Basus VJ]]
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[[Category: Toxin]]
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[[Category: Hawrot E]]
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[[Category: Song G]]

Current revision

NMR SOLUTION STRUCTURE OF AN ALPHA-BUNGAROTOXIN(SLASH)NICOTINIC RECEPTOR PEPTIDE COMPLEX

PDB ID 1abt

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