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1ctx

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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.
Method:	X-ray diffraction, Resolution 2.8Å
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

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 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 MD

@@ Line 1: / Line 1: @@
-[[Image:1ctx.gif|left|200px]]<br /><applet load="1ctx" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1ctx, resolution 2.8&Aring;" />
-'''THREE-DIMENSIONAL STRUCTURE OF THE-LONG-NEUROTOXIN FROM COBRA VENOM'''<br />
-==Overview==
+==THREE-DIMENSIONAL STRUCTURE OF THE-LONG-NEUROTOXIN FROM COBRA VENOM==
-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.
+<StructureSection load='1ctx' size='340' side='right'caption='[[1ctx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<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>
-CTX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Naja_siamensis Naja siamensis]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CTX OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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>
-==Reference==
+</table>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=6930640 6930640]
+== Function ==
+[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>
+== 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/ct/1ctx_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=1ctx ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Naja siamensis]]
-[[Category: Single protein]]
+[[Category: Saenger W]]
-[[Category: Saenger, W.]]
+[[Category: Walkinshaw MD]]
-[[Category: Walkinshaw, M.D.]]
-[[Category: toxin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:45:27 2007''

1ctx

From Proteopedia

Current revision

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

Structural highlights

Function

Evolutionary Conservation

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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