1idh: Difference between revisions

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-[[Image:1idh.gif|left|200px]]<br /><applet load="1idh" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1idh" />
-'''THE NMR SOLUTION STRUCTURE OF THE COMPLEX FORMED BETWEEN ALPHA-BUNGAROTOXIN AND AN 18MER COGNATE PEPTIDE'''<br />
-==Overview==
+==THE NMR SOLUTION STRUCTURE OF THE COMPLEX FORMED BETWEEN ALPHA-BUNGAROTOXIN AND AN 18MER COGNATE PEPTIDE==
-The region encompassing residues 181-98 on the alpha1 subunit of the, muscle-type nicotinic acetylcholine receptor forms a major determinant for, the binding of alpha-neurotoxins. We have prepared an (15)N-enriched, 18-amino acid peptide corresponding to the sequence in this region to, facilitate structural elucidation by multidimensional NMR. Our aim was to, determine the structural basis for the high affinity, stoichiometric, complex formed between this cognate peptide and alpha-bungarotoxin, a long, alpha-neurotoxin. Resonances in the complex were assigned through, heteronuclear and homonuclear NMR experiments, and the resulting, interproton distance constraints were used to generate ensemble structures, of the complex. Thr(8), Pro(10), Lys(38), Val(39), Val(40), and Pro(69) in, alpha-bungarotoxin and Tyr(189), Tyr(190), Thr(191), Cys(192), Asp(195), and Thr(196) in the peptide participate in major intermolecular contacts., A comparison of the free and bound alpha-bungarotoxin structures reveals, significant conformational rearrangements in flexible regions of, alpha-bungarotoxin, mainly loops I, II, and the C-terminal tail., Furthermore, several of the calculated structures suggest that cation-pi, interactions may be involved in binding. The root mean square deviation of, the polypeptide backbone in the complex is 2.07 A. This structure, provides, to date, the highest resolution description of the contacts, between a prototypic alpha-neurotoxin and its cognate recognition, sequence.
+<StructureSection load='1idh' size='340' side='right'caption='[[1idh]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1idh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] and [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IDH FirstGlance]. <br>
+</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</scene></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=1idh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1idh OCA], [https://pdbe.org/1idh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1idh RCSB], [https://www.ebi.ac.uk/pdbsum/1idh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1idh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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 ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/id/1idh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1idh ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-IDH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bungarus_multicinctus Bungarus multicinctus] and [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IDH OCA].
+*[[Bungarotoxin 3D structures|Bungarotoxin 3D structures]]
+== References ==
-==Reference==
+<references/>
-The solution structure of the complex formed between alpha-bungarotoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica., Zeng H, Moise L, Grant MA, Hawrot E, J Biol Chem. 2001 Jun 22;276(25):22930-40. Epub 2001 Apr 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11312275 11312275]
+__TOC__
+</StructureSection>
 [[Category: Bungarus multicinctus]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Torpedo californica]]
+[[Category: Tetronarce californica]]
-[[Category: Grant, M.A.]]
+[[Category: Grant MA]]
-[[Category: Hawrot, E.]]
+[[Category: Hawrot E]]
-[[Category: Moise, L.]]
+[[Category: Moise L]]
-[[Category: Zeng, H.]]
+[[Category: Zeng H]]
-[[Category: alpha 1 subunit]]
-[[Category: alpha-bungarotoxin]]
-[[Category: cation-pi interaction]]
-[[Category: nicotinic acetylcholine receptor]]
-[[Category: nmr]]
-[[Category: protein-protein interaction]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 17:18:51 2007''