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1ctx

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[[Image:1ctx.gif|left|200px]]
 
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==THREE-DIMENSIONAL STRUCTURE OF THE-LONG-NEUROTOXIN FROM COBRA VENOM==
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The line below this paragraph, containing "STRUCTURE_1ctx", creates the "Structure Box" on the page.
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<StructureSection load='1ctx' size='340' side='right'caption='[[1ctx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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</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>
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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=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>
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{{STRUCTURE_1ctx| PDB=1ctx | SCENE= }}
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</table>
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== Function ==
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'''THREE-DIMENSIONAL STRUCTURE OF THE-LONG-NEUROTOXIN FROM COBRA VENOM'''
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Overview==
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Check<jmol>
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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.
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ct/1ctx_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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1CTX is a [[Single protein]] structure of 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].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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</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].
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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://www.ncbi.nlm.nih.gov/pubmed/6930640 6930640]
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Naja siamensis]]
[[Category: Naja siamensis]]
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[[Category: Single protein]]
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[[Category: Saenger W]]
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[[Category: Saenger, W.]]
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[[Category: Walkinshaw MD]]
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[[Category: Walkinshaw, M D.]]
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[[Category: Toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:06:26 2008''
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Current revision

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

PDB ID 1ctx

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