1rgj: Difference between revisions

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[[Image:1rgj.png|left|200px]]


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==NMR STRUCTURE OF THE COMPLEX BETWEEN ALPHA-BUNGAROTOXIN AND MIMOTOPE OF THE NICOTINIC ACETYLCHOLINE RECEPTOR WITH ENHANCED ACTIVITY==
The line below this paragraph, containing "STRUCTURE_1rgj", creates the "Structure Box" on the page.
<StructureSection load='1rgj' size='340' side='right'caption='[[1rgj]]' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
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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=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>
{{STRUCTURE_1rgj|  PDB=1rgj  |  SCENE=  }}
</table>
 
== Function ==
===NMR STRUCTURE OF THE COMPLEX BETWEEN ALPHA-BUNGAROTOXIN AND MIMOTOPE OF THE NICOTINIC ACETILCHOLINE RECEPTOR WITH ENHANCED ACTIVITY===
[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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==About this Structure==
</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].
[[1rgj]] is a 2 chain structure of [[Bungarotoxin]] 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].  
<div style="clear:both"></div>


==See Also==
==See Also==
*[[Bungarotoxin]]
*[[Bungarotoxin 3D structures|Bungarotoxin 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:15178256</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Bungarus multicinctus]]
[[Category: Bungarus multicinctus]]
[[Category: Bernini, A.]]
[[Category: Large Structures]]
[[Category: Bracci, L.]]
[[Category: Bernini A]]
[[Category: Ciutti, A.]]
[[Category: Bracci L]]
[[Category: Lelli, B.]]
[[Category: Ciutti A]]
[[Category: Lozzi, L.]]
[[Category: Lelli B]]
[[Category: Neri, P.]]
[[Category: Lozzi L]]
[[Category: Niccolai, N.]]
[[Category: Neri P]]
[[Category: Scarselli, M.]]
[[Category: Niccolai N]]
[[Category: Spiga, O.]]
[[Category: Scarselli M]]
[[Category: Alpha-bungarotoxin]]
[[Category: Spiga O]]
[[Category: Beta-strand]]
[[Category: Neurotoxin]]
[[Category: Protein-peptide complex]]

Latest revision as of 11:23, 1 May 2024

NMR STRUCTURE OF THE COMPLEX BETWEEN ALPHA-BUNGAROTOXIN AND MIMOTOPE OF THE NICOTINIC ACETYLCHOLINE RECEPTOR WITH ENHANCED ACTIVITYNMR STRUCTURE OF THE COMPLEX BETWEEN ALPHA-BUNGAROTOXIN AND MIMOTOPE OF THE NICOTINIC ACETYLCHOLINE RECEPTOR WITH ENHANCED ACTIVITY

Structural highlights

1rgj is a 2 chain structure with sequence from Bungarus multicinctus. This structure supersedes the now removed PDB entry 1p67. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[1] [2] [3] [4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ McCann CM, Bracamontes J, Steinbach JH, Sanes JR. The cholinergic antagonist alpha-bungarotoxin also binds and blocks a subset of GABA receptors. Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5149-54. doi:, 10.1073/pnas.0600847103. Epub 2006 Mar 20. PMID:16549768 doi:http://dx.doi.org/10.1073/pnas.0600847103
  2. ↑ Hannan S, Mortensen M, Smart TG. Snake neurotoxin alpha-bungarotoxin is an antagonist at native GABA(A) receptors. Neuropharmacology. 2015 Jun;93:28-40. doi: 10.1016/j.neuropharm.2015.01.001. Epub, 2015 Jan 26. PMID:25634239 doi:http://dx.doi.org/10.1016/j.neuropharm.2015.01.001
  3. ↑ Servent D, Winckler-Dietrich V, Hu HY, Kessler P, Drevet P, Bertrand D, Menez A. Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem. 1997 Sep 26;272(39):24279-86. PMID:9305882
  4. ↑ Dajas-Bailador F, Costa G, Dajas F, Emmett S. Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo. Neurochem Int. 1998 Oct;33(4):307-12. PMID:9840221
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