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1pjv

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{{STRUCTURE_1pjv| PDB=1pjv | SCENE= }}
{{STRUCTURE_1pjv| PDB=1pjv | SCENE= }}
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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, 3-D Structure in Solution, Pharmacology and Docking on K+ channels===
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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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{{ABSTRACT_PUBMED_14498829}}
==About this Structure==
==About this Structure==
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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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1PJV is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PJV OCA].
==Reference==
==Reference==
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[[Category: Molecular modeling]]
[[Category: Molecular modeling]]
[[Category: Scorpion toxin]]
[[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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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:52:47 2008''

Revision as of 04:52, 28 July 2008

Image:1pjv.png

Template:STRUCTURE 1pjv

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

Template:ABSTRACT PUBMED 14498829

About this Structure

1PJV is a Single protein structure. Full experimental information is available from OCA.

Reference

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

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