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==NMR Structure of the Complex Between alpha-bungarotoxin and a Mimotope of the Nicotinic Acetylcholine Receptor==
==NMR Structure of the Complex Between alpha-bungarotoxin and a Mimotope of the Nicotinic Acetylcholine Receptor==
<StructureSection load='1jbd' size='340' side='right'caption='[[1jbd]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
<StructureSection load='1jbd' size='340' side='right'caption='[[1jbd]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1jbd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1hn7 1hn7]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JBD FirstGlance]. <br>
<table><tr><td colspan='2'>[[1jbd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1hn7 1hn7]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JBD 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;'>[[1hn7|1hn7]], [[1hoy|1hoy]], [[1ik8|1ik8]], [[1ikc|1ikc]]</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=1jbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jbd OCA], [https://pdbe.org/1jbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jbd RCSB], [https://www.ebi.ac.uk/pdbsum/1jbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jbd 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=1jbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jbd OCA], [https://pdbe.org/1jbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jbd RCSB], [https://www.ebi.ac.uk/pdbsum/1jbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jbd ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/NXL1A_BUNMU NXL1A_BUNMU]] Binds with high affinity to muscular and neuronal (alpha-7, alpha-8, and alpha-9) nicotinic acetylcholine receptors. Produces peripheral paralysis by blocking neuromuscular transmission at the postsynaptic site. Blocks the extracellular increase of dopamine evoked by nicotine only at the higher dose (4.2 uM).<ref>PMID:9305882</ref> <ref>PMID:9840221</ref>
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1jbd ConSurf].
</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=1jbd ConSurf].
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A combinatorial library approach was used to produce synthetic peptides mimicking the snake neurotoxin binding site of nicotinic receptors. Among the sequences, which inhibited binding of alpha-bungarotoxin to muscle and neuronal nicotinic receptors, HRYYESSLPWYPD, a 14-amino acid peptide with considerably higher toxin-binding affinity than the other synthesized peptides, was selected, and the structure of its complex with the toxin was analyzed by NMR. Comparison of the solution structure of the free toxin and its complex with this peptide indicated that complex formation induced extensive conformational rearrangements mainly at finger II and the carboxy terminus of the protein. The peptidyl residues P10 and Y4 seemed to be critical for peptide folding and complex stability, respectively. The latter residue of the peptide strongly interacted with the protein by entering a small pocket delimited by D30, C33, S34, R36, and V39 toxin side chains.
NMR structure of alpha-bungarotoxin free and bound to a mimotope of the nicotinic acetylcholine receptor.,Scarselli M, Spiga O, Ciutti A, Bernini A, Bracci L, Lelli B, Lozzi L, Calamandrei D, Di Maro D, Klein S, Niccolai N Biochemistry. 2002 Feb 5;41(5):1457-63. PMID:11814338<ref>PMID:11814338</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1jbd" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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[[Category: Bungarus multicinctus]]
[[Category: Bungarus multicinctus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bernini, A]]
[[Category: Bernini A]]
[[Category: Bracci, L]]
[[Category: Bracci L]]
[[Category: Calamandrei, D]]
[[Category: Calamandrei D]]
[[Category: Ciutti, A]]
[[Category: Ciutti A]]
[[Category: Klein, S]]
[[Category: Di Maro D]]
[[Category: Lelli, B]]
[[Category: Klein S]]
[[Category: Lozzi, L]]
[[Category: Lelli B]]
[[Category: Maro, D Di]]
[[Category: Lozzi L]]
[[Category: Niccolai, N]]
[[Category: Niccolai N]]
[[Category: Scarselli, M]]
[[Category: Scarselli M]]
[[Category: Spiga, O]]
[[Category: Spiga O]]
[[Category: Achr]]
[[Category: Alpha-bungarotoxin]]
[[Category: Protein-peptide complex]]
[[Category: Toxin]]

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