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1kfh

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(New page: 200px<br /><applet load="1kfh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kfh" /> '''Solution Structure of alpha-Bungarotoxin by ...)
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[[Image:1kfh.jpg|left|200px]]<br /><applet load="1kfh" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1kfh" />
 
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'''Solution Structure of alpha-Bungarotoxin by NMR Spectroscopy'''<br />
 
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==Overview==
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==Solution Structure of alpha-Bungarotoxin by NMR Spectroscopy==
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We report a new, higher resolution NMR structure of alpha-bungarotoxin, that defines the structure-determining disulfide core and beta-sheet, regions. We further report the NMR structure of the stoichiometric complex, formed between alpha-bungarotoxin and a recombinantly expressed 19-mer, peptide ((178)IPGKRTESFYECCKEPYPD(196)) derived from the alpha7 subunit of, the chick neuronal nicotinic acetylcholine receptor. A comparison of these, two structures reveals binding-induced stabilization of the flexible tip, of finger II in alpha-bungarotoxin. The conformational rearrangements in, the toxin create an extensive binding surface involving both sides of the, alpha7 19-mer hairpin-like structure. At the contact zone, Ala(7), Ser(9), and Ile(11) in finger I and Arg(36), Lys(38), Val(39), and Val(40) in, finger II of alpha-bungarotoxin interface with Phe(186), Tyr(187), Glu(188), and Tyr(194) in the alpha7 19-mer underscoring the importance of, receptor aromatic residues as critical neurotoxin-binding determinants., Superimposing the structure of the complex onto that of the, acetylcholine-binding protein (1I9B), a soluble homologue of the, extracellular domain of the alpha7 receptor, places alpha-bungarotoxin at, the peripheral surface of the inter-subunit interface occluding the, agonist-binding site. The disulfide-rich core of alpha-bungarotoxin is, suggested to be tilted in the direction of the membrane surface with, finger II extending into the proposed ligand-binding cavity.
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<StructureSection load='1kfh' size='340' side='right'caption='[[1kfh]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1kfh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KFH 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</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=1kfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kfh OCA], [https://pdbe.org/1kfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kfh RCSB], [https://www.ebi.ac.uk/pdbsum/1kfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kfh ProSAT]</span></td></tr>
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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/kf/1kfh_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1kfh ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1KFH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KFH OCA].
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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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NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor., Moise L, Piserchio A, Basus VJ, Hawrot E, J Biol Chem. 2002 Apr 5;277(14):12406-17. Epub 2002 Jan 14. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11790782 11790782]
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__TOC__
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</StructureSection>
[[Category: Bungarus multicinctus]]
[[Category: Bungarus multicinctus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Basus, V.J.]]
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[[Category: Basus VJ]]
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[[Category: Hawrot, E.]]
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[[Category: Hawrot E]]
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[[Category: Moise, L.]]
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[[Category: Moise L]]
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[[Category: Piserchio, A.]]
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[[Category: Piserchio A]]
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[[Category: alpha-bungarotoxin]]
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[[Category: long snake neurotoxin]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:09:52 2007''
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Current revision

Solution Structure of alpha-Bungarotoxin by NMR Spectroscopy

PDB ID 1kfh

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