1lxh

From Proteopedia

(Difference between revisions)

Revision as of 06:50, 18 August 2021

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

Structural highlights

1lxh is a 2 chain structure with sequence from Naja kaouthia and Pacific electric ray. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	1lxg
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NXL1_NAJKA] The monomeric form binds with high affinity to muscular, Torpedo (muscle-type), and neuronal alpha-7 nicotinic acetylcholine receptors (nAChR). Has no effect on alpha-3/beta-2 nAChR. Causes paralysis by preventing acetylcholine binding to the nAChR. Does not show any blockade of the nicotine-evoked release of dopamine and does not affect ACh release. In mice lung cancer, causes reduction of tumor growth.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] The homodimeric form binds with low affinity to Torpedo (muscle-type) and alpha-7 nAChRs, whereas it acquires the capacity to block alpha-3/beta-2 nAChRs.^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17] ^[18] [ACHA_TORCA] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Evolutionary Conservation

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

Publication Abstract from PubMed

The alpha18-mer peptide, spanning residues 181-198 of the Torpedo nicotinic acetylcholine receptor alpha1 subunit, contains key binding determinants for agonists and competitive antagonists. To investigate whether the alpha18-mer can bind other alpha-neurotoxins besides alpha-bungarotoxin, we designed a two-dimensional (1)H-(15)N heteronuclear single quantum correlation experiment to screen four related neurotoxins for their binding ability to the peptide. Of the four toxins tested (erabutoxin a, erabutoxin b, LSIII, and alpha-cobratoxin), only alpha-cobratoxin binds the alpha18-mer to form a 1:1 complex. The NMR solution structure of the alpha-cobratoxin.alpha18-mer complex was determined with a backbone root mean square deviation of 1.46 A. In the structure, alpha-cobratoxin contacts the alpha18-mer at the tips of loop I and II and through C-terminal cationic residues. The contact zone derived from the intermolecular nuclear Overhauser effects is in agreement with recent biochemical data. Furthermore, the structural models support the involvement of cation-pi interactions in stabilizing the complex. In addition, the binding screen results suggest that C-terminal cationic residues of alpha-bungarotoxin and alpha-cobratoxin contribute significantly to binding of the alpha18-mer. Finally, we present a structural model for nicotinic acetylcholine receptor-alpha-cobratoxin interaction by superimposing the alpha-cobratoxin.alpha18-mer complex onto the crystal structure of the acetylcholine-binding protein (Protein Data Bank code ).

NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica.,Zeng H, Hawrot E J Biol Chem. 2002 Oct 4;277(40):37439-45. Epub 2002 Jul 19. PMID:12133834^[19]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ Kang S, Maelicke A. Fluorescein isothiocyanate-labeled alpha-cobratoxin. Biochemical characterization and interaction with acetylcholine receptor from Electrophorus electricus. J Biol Chem. 1980 Aug 10;255(15):7326-32. PMID:6771288
↑ Martin BM, Chibber BA, Maelicke A. The sites of neurotoxicity in alpha-cobratoxin. J Biol Chem. 1983 Jul 25;258(14):8714-22. PMID:6553056
↑ Alkondon M, Albuquerque EX. alpha-Cobratoxin blocks the nicotinic acetylcholine receptor in rat hippocampal neurons. Eur J Pharmacol. 1990 Dec 4;191(3):505-6. PMID:2086254
↑ Apel C, Ricny J, Wagner G, Wessler I. alpha-Bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;352(6):646-52. PMID:9053737
↑ 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
↑ 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
↑ Antil S, Servent D, Menez A. Variability among the sites by which curaremimetic toxins bind to torpedo acetylcholine receptor, as revealed by identification of the functional residues of alpha-cobratoxin. J Biol Chem. 1999 Dec 3;274(49):34851-8. PMID:10574958
↑ Grozio A, Paleari L, Catassi A, Servent D, Cilli M, Piccardi F, Paganuzzi M, Cesario A, Granone P, Mourier G, Russo P. Natural agents targeting the alpha7-nicotinic-receptor in NSCLC: a promising prospective in anti-cancer drug development. Int J Cancer. 2008 Apr 15;122(8):1911-5. PMID:18067132 doi:http://dx.doi.org/10.1002/ijc.23298
↑ 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
↑ Kang S, Maelicke A. Fluorescein isothiocyanate-labeled alpha-cobratoxin. Biochemical characterization and interaction with acetylcholine receptor from Electrophorus electricus. J Biol Chem. 1980 Aug 10;255(15):7326-32. PMID:6771288
↑ Martin BM, Chibber BA, Maelicke A. The sites of neurotoxicity in alpha-cobratoxin. J Biol Chem. 1983 Jul 25;258(14):8714-22. PMID:6553056
↑ Alkondon M, Albuquerque EX. alpha-Cobratoxin blocks the nicotinic acetylcholine receptor in rat hippocampal neurons. Eur J Pharmacol. 1990 Dec 4;191(3):505-6. PMID:2086254
↑ Apel C, Ricny J, Wagner G, Wessler I. alpha-Bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;352(6):646-52. PMID:9053737
↑ 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
↑ 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
↑ Antil S, Servent D, Menez A. Variability among the sites by which curaremimetic toxins bind to torpedo acetylcholine receptor, as revealed by identification of the functional residues of alpha-cobratoxin. J Biol Chem. 1999 Dec 3;274(49):34851-8. PMID:10574958
↑ Grozio A, Paleari L, Catassi A, Servent D, Cilli M, Piccardi F, Paganuzzi M, Cesario A, Granone P, Mourier G, Russo P. Natural agents targeting the alpha7-nicotinic-receptor in NSCLC: a promising prospective in anti-cancer drug development. Int J Cancer. 2008 Apr 15;122(8):1911-5. PMID:18067132 doi:http://dx.doi.org/10.1002/ijc.23298
↑ Zeng H, Hawrot E. NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica. J Biol Chem. 2002 Oct 4;277(40):37439-45. Epub 2002 Jul 19. PMID:12133834 doi:10.1074/jbc.M205483200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1lxh"

@@ Line 3: / Line 3: @@
 <StructureSection load='1lxh' size='340' side='right'caption='[[1lxh]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1lxh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] and [http://en.wikipedia.org/wiki/Pacific_electric_ray Pacific electric ray]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LXH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1lxh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] and [https://en.wikipedia.org/wiki/Pacific_electric_ray Pacific electric ray]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXH FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lxg|1lxg]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lxg|1lxg]]</div></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=1lxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxh OCA], [http://pdbe.org/1lxh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1lxh RCSB], [http://www.ebi.ac.uk/pdbsum/1lxh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxh 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=1lxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxh OCA], [https://pdbe.org/1lxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxh RCSB], [https://www.ebi.ac.uk/pdbsum/1lxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxh ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NXL1_NAJKA NXL1_NAJKA]] The monomeric form binds with high affinity to muscular, Torpedo (muscle-type), and neuronal alpha-7 nicotinic acetylcholine receptors (nAChR). Has no effect on alpha-3/beta-2 nAChR. Causes paralysis by preventing acetylcholine binding to the nAChR. Does not show any blockade of the nicotine-evoked release of dopamine and does not affect ACh release. In mice lung cancer, causes reduction of tumor growth.<ref>PMID:18381281</ref> <ref>PMID:6771288</ref> <ref>PMID:6553056</ref> <ref>PMID:2086254</ref> <ref>PMID:9053737</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref> <ref>PMID:10574958</ref> <ref>PMID:18067132</ref>   The homodimeric form binds with low affinity to Torpedo (muscle-type) and alpha-7 nAChRs, whereas it acquires the capacity to block alpha-3/beta-2 nAChRs.<ref>PMID:18381281</ref> <ref>PMID:6771288</ref> <ref>PMID:6553056</ref> <ref>PMID:2086254</ref> <ref>PMID:9053737</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref> <ref>PMID:10574958</ref> <ref>PMID:18067132</ref>  [[http://www.uniprot.org/uniprot/ACHA_TORCA ACHA_TORCA]] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
+[[https://www.uniprot.org/uniprot/NXL1_NAJKA NXL1_NAJKA]] The monomeric form binds with high affinity to muscular, Torpedo (muscle-type), and neuronal alpha-7 nicotinic acetylcholine receptors (nAChR). Has no effect on alpha-3/beta-2 nAChR. Causes paralysis by preventing acetylcholine binding to the nAChR. Does not show any blockade of the nicotine-evoked release of dopamine and does not affect ACh release. In mice lung cancer, causes reduction of tumor growth.<ref>PMID:18381281</ref> <ref>PMID:6771288</ref> <ref>PMID:6553056</ref> <ref>PMID:2086254</ref> <ref>PMID:9053737</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref> <ref>PMID:10574958</ref> <ref>PMID:18067132</ref>   The homodimeric form binds with low affinity to Torpedo (muscle-type) and alpha-7 nAChRs, whereas it acquires the capacity to block alpha-3/beta-2 nAChRs.<ref>PMID:18381281</ref> <ref>PMID:6771288</ref> <ref>PMID:6553056</ref> <ref>PMID:2086254</ref> <ref>PMID:9053737</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref> <ref>PMID:10574958</ref> <ref>PMID:18067132</ref>  [[https://www.uniprot.org/uniprot/ACHA_TORCA ACHA_TORCA]] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1lxh

From Proteopedia

Revision as of 06:50, 18 August 2021

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox