1lxg: Difference between revisions

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


{{STRUCTURE_1lxg|  PDB=1lxg  |  SCENE=  }}
==Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)==
 
<StructureSection load='1lxg' size='340' side='right'caption='[[1lxg]]' scene=''>
===Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)===
== Structural highlights ==
 
<table><tr><td colspan='2'>[[1lxg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] 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=1LXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXG FirstGlance]. <br>
{{ABSTRACT_PUBMED_12133834}}
</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>
==About this Structure==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxg OCA], [https://pdbe.org/1lxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxg RCSB], [https://www.ebi.ac.uk/pdbsum/1lxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxg ProSAT]</span></td></tr>
[[1lxg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] and [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXG OCA].  
</table>
 
== Function ==
==Reference==
[https://www.uniprot.org/uniprot/3L21_NAJKA 3L21_NAJKA] Monomer: binds with high affinity to muscular (alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND) nAChR (tested on Torpedo californica, Kd=0.2-4.5 nM) and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (Kd=13-105 nM) (PubMed:18381281, PubMed:9305882, PubMed:22223648). Also inhibits GABA(A) channels (PubMed:26221036). Heteropentamer targets studied are composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits (IC(50)=236 nM), alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits (IC(50)=469 nM), alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits (IC(50)=485 nM), alpha-5-beta-3-gamma-2 (GABRA5-GABRB3-GABRG2) subunits (IC(50)=635 nM), and alpha-2-beta-3-gamma-2 (GABRA2-GABRB3-GABRG2) subunits (IC(50)=1099 nM) (activated by 10 uM GABA) (PubMed:26221036).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref> <ref>PMID:26221036</ref> <ref>PMID:30025921</ref>  Homodimer: binds with high affinity (but lower than the monomeric form) to muscular (IC(50)=9.7 nM) and with low affinity to neuronal alpha-7/CHRNA7 nAChRs (IC(50)=1370 nM) (PubMed:22223648). However, it acquires (compared to the monomeric form) the capacity to block alpha-3/beta-2 (CHRNA3/CHRNB2) nAChRs (PubMed:18381281).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref>  Heterodimer with cytotoxin 3 (AC P01446): is slightly more active than the homodimer in inhibiting alpha-7/CHRNA7 nAChR and is considerably more active in blocking the alpha-3-beta-2/CHRNA3-CHRNB2 nAChR.<ref>PMID:22223648</ref>
<ref group="xtra">PMID:012133834</ref><references group="xtra"/>
== 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/lx/1lxg_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=1lxg ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Naja kaouthia]]
[[Category: Naja kaouthia]]
[[Category: Torpedo californica]]
[[Category: Tetronarce californica]]
[[Category: Hawrot, E.]]
[[Category: Hawrot E]]
[[Category: Zeng, H.]]
[[Category: Zeng H]]
[[Category: Alpha-cobratoxin]]
[[Category: Nicotinic acetylcholine receptor]]
[[Category: Protein-protein interaction]]
[[Category: Toxin]]

Latest revision as of 11:29, 10 April 2024

Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)Solution structure of alpha-cobratoxin complexed with a cognate peptide (structure ensemble)

Structural highlights

1lxg is a 2 chain structure with sequence from Naja kaouthia and Tetronarce californica. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

3L21_NAJKA Monomer: binds with high affinity to muscular (alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND) nAChR (tested on Torpedo californica, Kd=0.2-4.5 nM) and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (Kd=13-105 nM) (PubMed:18381281, PubMed:9305882, PubMed:22223648). Also inhibits GABA(A) channels (PubMed:26221036). Heteropentamer targets studied are composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits (IC(50)=236 nM), alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits (IC(50)=469 nM), alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits (IC(50)=485 nM), alpha-5-beta-3-gamma-2 (GABRA5-GABRB3-GABRG2) subunits (IC(50)=635 nM), and alpha-2-beta-3-gamma-2 (GABRA2-GABRB3-GABRG2) subunits (IC(50)=1099 nM) (activated by 10 uM GABA) (PubMed:26221036).[1] [2] [3] [4] Homodimer: binds with high affinity (but lower than the monomeric form) to muscular (IC(50)=9.7 nM) and with low affinity to neuronal alpha-7/CHRNA7 nAChRs (IC(50)=1370 nM) (PubMed:22223648). However, it acquires (compared to the monomeric form) the capacity to block alpha-3/beta-2 (CHRNA3/CHRNB2) nAChRs (PubMed:18381281).[5] [6] Heterodimer with cytotoxin 3 (AC P01446): is slightly more active than the homodimer in inhibiting alpha-7/CHRNA7 nAChR and is considerably more active in blocking the alpha-3-beta-2/CHRNA3-CHRNB2 nAChR.[7]

Evolutionary Conservation

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

References

  1. ↑ Osipov AV, Kasheverov IE, Makarova YV, Starkov VG, Vorontsova OV, Ziganshin RKh, Andreeva TV, Serebryakova MV, Benoit A, Hogg RC, Bertrand D, Tsetlin VI, Utkin YN. Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification. J Biol Chem. 2008 May 23;283(21):14571-80. Epub 2008 Apr 1. PMID:18381281 doi:http://dx.doi.org/M802085200
  2. ↑ Osipov AV, Rucktooa P, Kasheverov IE, Filkin SY, Starkov VG, Andreeva TV, Sixma TK, Bertrand D, Utkin YN, Tsetlin VI. Dimeric alpha-cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors. J Biol Chem. 2012 Feb 24;287(9):6725-34. Epub 2012 Jan 5. PMID:22223648 doi:10.1074/jbc.M111.322313
  3. ↑ Kudryavtsev DS, Shelukhina IV, Son LV, Ojomoko LO, Kryukova EV, Lyukmanova EN, Zhmak MN, Dolgikh DA, Ivanov IA, Kasheverov IE, Starkov VG, Ramerstorfer J, Sieghart W, Tsetlin VI, Utkin YN. Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors. J Biol Chem. 2015 Sep 11;290(37):22747-58. PMID:26221036 doi:10.1074/jbc.M115.648824
  4. ↑ Yu J, Zhu X, Zhang L, Kudryavtsev D, Kasheverov I, Lei Y, Zhangsun D, Tsetlin V, Luo S. Species specificity of rat and human α7 nicotinic acetylcholine receptors towards different classes of peptide and protein antagonists. Neuropharmacology. 2018 Sep 1;139:226-237. PMID:30025921 doi:10.1016/j.neuropharm.2018.07.019
  5. ↑ Osipov AV, Kasheverov IE, Makarova YV, Starkov VG, Vorontsova OV, Ziganshin RKh, Andreeva TV, Serebryakova MV, Benoit A, Hogg RC, Bertrand D, Tsetlin VI, Utkin YN. Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification. J Biol Chem. 2008 May 23;283(21):14571-80. Epub 2008 Apr 1. PMID:18381281 doi:http://dx.doi.org/M802085200
  6. ↑ Osipov AV, Rucktooa P, Kasheverov IE, Filkin SY, Starkov VG, Andreeva TV, Sixma TK, Bertrand D, Utkin YN, Tsetlin VI. Dimeric alpha-cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors. J Biol Chem. 2012 Feb 24;287(9):6725-34. Epub 2012 Jan 5. PMID:22223648 doi:10.1074/jbc.M111.322313
  7. ↑ Osipov AV, Rucktooa P, Kasheverov IE, Filkin SY, Starkov VG, Andreeva TV, Sixma TK, Bertrand D, Utkin YN, Tsetlin VI. Dimeric alpha-cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors. J Biol Chem. 2012 Feb 24;287(9):6725-34. Epub 2012 Jan 5. PMID:22223648 doi:10.1074/jbc.M111.322313
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