1pjv

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[[Image:1pjv.jpg|left|200px]]
 
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==Cobatoxin 1 from Centruroides noxius Scorpion venom: Chemical Synthesis, 3-D Structure in Solution, Pharmacology and Docking on K+ channels==
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The line below this paragraph, containing "STRUCTURE_1pjv", creates the "Structure Box" on the page.
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<StructureSection load='1pjv' size='340' side='right'caption='[[1pjv]]' 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'>[[1pjv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Centruroides_noxius Centruroides noxius]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PJV FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1pjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pjv OCA], [https://pdbe.org/1pjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pjv RCSB], [https://www.ebi.ac.uk/pdbsum/1pjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pjv ProSAT]</span></td></tr>
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{{STRUCTURE_1pjv| PDB=1pjv | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KA101_CENNO KA101_CENNO] Blocks Shaker B (Sh) and voltage-gated potassium-channels Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3. Also inhibits small conductance calcium-activated potassium channels (KCNN) and intermediate conductance calcium-activated potassium channel (KCa3.1/KCNN4).<ref>PMID:14498829</ref> <ref>PMID:9688256</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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CoTX1 (cobatoxin 1) is a 32-residue toxin with three disulphide bridges that has been isolated from the venom of the Mexican scorpion Centruroides noxius Hoffmann. Here we report the chemical synthesis, disulphide bridge organization, 3-D (three-dimensional) solution structure determination, pharmacology on K+ channel subtypes (voltage-gated and Ca2+-activated) and docking-simulation experiments. An enzyme-based cleavage of the synthetic folded/oxidized CoTX1 indicated half-cystine pairs between Cys3-Cys22, Cys8-Cys27 and Cys12-Cys29. The 3-D structure of CoTX1 (solved by 1H-NMR) showed that it folds according to the common alpha/beta scaffold of scorpion toxins. In vivo, CoTX1 was lethal after intracerebroventricular injection to mice (LD50 value of 0.5 microg/mouse). In vitro, CoTX1 tested on cells expressing various voltage-gated or Ca2+-activated (IKCa1) K+ channels showed potent inhibition of currents from rat K(v)1.2 ( K(d) value of 27 nM). CoTX1 also weakly competed with 125I-labelled apamin for binding to SKCa channels (small-conductance Ca2+-activated K+ channels) on rat brain synaptosomes (IC50 value of 7.2 microM). The 3-D structure of CoTX1 was used in docking experiments which suggests a key role of Arg6 or Lys10, Arg14, Arg18, Lys21 (dyad), Ile23, Asn24, Lys28 and Tyr30 (dyad) residues of CoTX1 in its interaction with the rat K(v)1.2 channel. In addition, a [Pro7,Gln9]-CoTX1 analogue (ACoTX1) was synthesized. The two residue replacements were selected aiming to restore the RPCQ motif in order to increase peptide affinity towards SKCa channels, and to alter the CoTX1 dipole moment such that it is expected to decrease peptide activity on K(v) channels. Unexpectedly, ACoTX1 exhibited an activity similar to that of CoTX1 towards SKCa channels, while it was markedly more potent on IKCa1 and several voltage-gated K+ channels.
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'''Cobatoxin 1 from Centruroides noxius Scorpion venom: Chemical Synthesis, 3-D Structure in Solution, Pharmacology and Docking on K+ channels'''
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Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels.,Jouirou B, Mosbah A, Visan V, Grissmer S, M'Barek S, Fajloun Z, Van Rietschoten J, Devaux C, Rochat H, Lippens G, El Ayeb M, De Waard M, Mabrouk K, Sabatier JM Biochem J. 2004 Jan 1;377(Pt 1):37-49. PMID:14498829<ref>PMID:14498829</ref>
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==Overview==
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CoTX1 (cobatoxin 1) is a 32-residue toxin with three disulphide bridges that has been isolated from the venom of the Mexican scorpion Centruroides noxius Hoffmann. Here we report the chemical synthesis, disulphide bridge organization, 3-D (three-dimensional) solution structure determination, pharmacology on K+ channel subtypes (voltage-gated and Ca2+-activated) and docking-simulation experiments. An enzyme-based cleavage of the synthetic folded/oxidized CoTX1 indicated half-cystine pairs between Cys3-Cys22, Cys8-Cys27 and Cys12-Cys29. The 3-D structure of CoTX1 (solved by 1H-NMR) showed that it folds according to the common alpha/beta scaffold of scorpion toxins. In vivo, CoTX1 was lethal after intracerebroventricular injection to mice (LD50 value of 0.5 microg/mouse). In vitro, CoTX1 tested on cells expressing various voltage-gated or Ca2+-activated (IKCa1) K+ channels showed potent inhibition of currents from rat K(v)1.2 ( K(d) value of 27 nM). CoTX1 also weakly competed with 125I-labelled apamin for binding to SKCa channels (small-conductance Ca2+-activated K+ channels) on rat brain synaptosomes (IC50 value of 7.2 microM). The 3-D structure of CoTX1 was used in docking experiments which suggests a key role of Arg6 or Lys10, Arg14, Arg18, Lys21 (dyad), Ile23, Asn24, Lys28 and Tyr30 (dyad) residues of CoTX1 in its interaction with the rat K(v)1.2 channel. In addition, a [Pro7,Gln9]-CoTX1 analogue (ACoTX1) was synthesized. The two residue replacements were selected aiming to restore the RPCQ motif in order to increase peptide affinity towards SKCa channels, and to alter the CoTX1 dipole moment such that it is expected to decrease peptide activity on K(v) channels. Unexpectedly, ACoTX1 exhibited an activity similar to that of CoTX1 towards SKCa channels, while it was markedly more potent on IKCa1 and several voltage-gated K+ channels.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1PJV is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJV OCA].
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</div>
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<div class="pdbe-citations 1pjv" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels., Jouirou B, Mosbah A, Visan V, Grissmer S, M'Barek S, Fajloun Z, Van Rietschoten J, Devaux C, Rochat H, Lippens G, El Ayeb M, De Waard M, Mabrouk K, Sabatier JM, Biochem J. 2004 Jan 1;377(Pt 1):37-49. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14498829 14498829]
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*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
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[[Category: Single protein]]
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== References ==
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[[Category: Ayeb, M El.]]
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<references/>
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[[Category: Grissmer, S.]]
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__TOC__
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[[Category: Jouirou, B.]]
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</StructureSection>
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[[Category: Mabrouk, K.]]
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[[Category: Centruroides noxius]]
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[[Category: Mosbah, A.]]
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[[Category: Large Structures]]
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[[Category: Rochat, H.]]
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[[Category: De Waard M]]
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[[Category: Sabatier, J M.]]
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[[Category: El Ayeb M]]
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[[Category: Visan, V.]]
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[[Category: Grissmer S]]
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[[Category: Waard, M De.]]
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[[Category: Jouirou B]]
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[[Category: 1h-nmr spectroscopy]]
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[[Category: Mabrouk K]]
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[[Category: 3-d structure]]
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[[Category: Mosbah A]]
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[[Category: Centuroides noxius]]
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[[Category: Rochat H]]
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[[Category: Chemical synthesis]]
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[[Category: Sabatier JM]]
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[[Category: Circular dichroism]]
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[[Category: Visan V]]
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[[Category: Cobatoxin 1]]
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[[Category: Docking experiment]]
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[[Category: K+ channel]]
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[[Category: Molecular modeling]]
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[[Category: Scorpion toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:10:10 2008''
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Current revision

Cobatoxin 1 from Centruroides noxius Scorpion venom: Chemical Synthesis, 3-D Structure in Solution, Pharmacology and Docking on K+ channels

PDB ID 1pjv

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