1rgj: Difference between revisions

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 ==NMR STRUCTURE OF THE COMPLEX BETWEEN ALPHA-BUNGAROTOXIN AND MIMOTOPE OF THE NICOTINIC ACETYLCHOLINE RECEPTOR WITH ENHANCED ACTIVITY==
-<StructureSection load='1rgj' size='340' side='right'caption='[[1rgj]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
+<StructureSection load='1rgj' size='340' side='right'caption='[[1rgj]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1rgj]] is a 2 chain structure with sequence from [http://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=1p67 1p67]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RGJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1rgj]] 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=1p67 1p67]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RGJ FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jbd|1jbd]], [[1hoy|1hoy]], [[1ik8|1ik8]], [[1ikc|1ikc]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rgj OCA], [http://pdbe.org/1rgj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rgj RCSB], [http://www.ebi.ac.uk/pdbsum/1rgj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rgj 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=1rgj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rgj OCA], [https://pdbe.org/1rgj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rgj RCSB], [https://www.ebi.ac.uk/pdbsum/1rgj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rgj ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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 ==
 [[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=1rgj ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-The interaction between alpha-bungarotoxin and linear synthetic peptides, mimotope of the nicotinic acetylcholine receptor binding site, has been characterised extensively by several methods and a wealth of functional, kinetic and structural data are available. Hence, this system represents a suitable model to explore in detail the dynamics of a peptide-protein interaction. Here, the solution structure of a new complex of the protein toxin with a tridecapeptide ligand exhibiting high affinity has been determined by NMR. As observed for three other previously reported mimotope-alpha-bungarotoxin complexes, also in this case correlations between biological activity and kinetic data are not fully consistent with a static discussion of structural data. Molecular dynamics simulations of the four mimotope-toxin complexes indicate that a relevant contribution to the complex stability is given by the extent of the residual flexibility that the protein maintains upon peptide binding. This feature, limiting the entropy loss caused by protein folding and binding, ought to be generally considered in a rational design of specific protein ligands.
-NMR and MD studies on the interaction between ligand peptides and alpha-bungarotoxin.,Bernini A, Ciutti A, Spiga O, Scarselli M, Klein S, Vannetti S, Bracci L, Lozzi L, Lelli B, Falciani C, Neri P, Niccolai N J Mol Biol. 2004 Jun 18;339(5):1169-77. PMID:15178256<ref>PMID:15178256</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 1rgj" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 37: / Line 28: @@
 [[Category: Bungarus multicinctus]]
 [[Category: Large Structures]]
-[[Category: Bernini, A]]
+[[Category: Bernini A]]
-[[Category: Bracci, L]]
+[[Category: Bracci L]]
-[[Category: Ciutti, A]]
+[[Category: Ciutti A]]
-[[Category: Lelli, B]]
+[[Category: Lelli B]]
-[[Category: Lozzi, L]]
+[[Category: Lozzi L]]
-[[Category: Neri, P]]
+[[Category: Neri P]]
-[[Category: Niccolai, N]]
+[[Category: Niccolai N]]
-[[Category: Scarselli, M]]
+[[Category: Scarselli M]]
-[[Category: Spiga, O]]
+[[Category: Spiga O]]
-[[Category: Alpha-bungarotoxin]]
-[[Category: Beta-strand]]
-[[Category: Neurotoxin]]
-[[Category: Protein-peptide complex]]
-[[Category: Toxin]]