1ctx

From Proteopedia

(Difference between revisions)

Revision as of 10:40, 14 July 2021

THREE-DIMENSIONAL STRUCTURE OF THE-LONG-NEUROTOXIN FROM COBRA VENOM

Structural highlights

1ctx is a 1 chain structure with sequence from Naja siamensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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]

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 three-dimensional structure of alpha-cobra-toxin, the "long" neurotoxin from the venom of Naja naja siamensis, has been determined at 2.8-A resolution. Crystals grown as hexagonal needles have space group P6522 with unit cell parameters a = b = 74.59 A, c = 42.89 A; one molecule per asymmetric unit. Phases were determined with a single isomorphous derivative with HgI2 by using the anomalous scattering of the single-site HgI2 molecule to resolve the phase ambiguity. The polypeptide chain folds into three major loops and one tail emerging from a globular head. The protruding long central loop (residues 21-40) is flanked on either side by two shorter loops (residues 4-13 and 44-55); the tail piece (residues 63-71) hangs behind this loop. The molecular conformation is determined by four disulfides in the head and one at the tip of the long loop, by a triple-stranded beta-pleated sheet involving this loop, and by hydrophobic interactions stabilizing the other two loops. The structure of alpha-cobratoxin is compared to that described for the "short" erabutoxin b which shows similar arrangement of structurally and functionally invariant groups.

Three-dimensional structure of the "long" neurotoxin from cobra venom.,Walkinshaw MD, Saenger W, Maelicke A Proc Natl Acad Sci U S A. 1980 May;77(5):2400-4. PMID:6930640^[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
↑ Walkinshaw MD, Saenger W, Maelicke A. Three-dimensional structure of the "long" neurotoxin from cobra venom. Proc Natl Acad Sci U S A. 1980 May;77(5):2400-4. PMID:6930640

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/1ctx"

Categories: Large Structures | Naja siamensis | Saenger, W | Walkinshaw, M D | Toxin

@@ Line 3: / Line 3: @@
 <StructureSection load='1ctx' size='340' side='right'caption='[[1ctx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1ctx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_siamensis Naja siamensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CTX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CTX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1ctx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_siamensis Naja siamensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CTX FirstGlance]. <br>
-</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=1ctx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ctx OCA], [http://pdbe.org/1ctx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ctx RCSB], [http://www.ebi.ac.uk/pdbsum/1ctx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ctx ProSAT]</span></td></tr>
+</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=1ctx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ctx OCA], [https://pdbe.org/1ctx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ctx RCSB], [https://www.ebi.ac.uk/pdbsum/1ctx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ctx 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>
+[[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1ctx

From Proteopedia

Revision as of 10:40, 14 July 2021

THREE-DIMENSIONAL STRUCTURE OF THE-LONG-NEUROTOXIN FROM COBRA VENOM

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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