1b45

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1b45

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ALPHA-CNIA CONOTOXIN FROM CONUS CONSORS, NMR, 43 STRUCTURES

Overview

Two novel alpha-conotoxins were purified and characterized from the venom, of the fish-hunting cone snail Conus consors. These peptides were, identified by screening HPLC fractions of the crude venom and by binding, experiments with Torpedo nicotinic acetylcholine receptor. The toxins, named alpha-CnIA and alpha-CnIB exhibited sequences of 14 and 12 amino, acids, respectively. The alpha-CnIA represents the main alpha-conotoxin, contained in the venom, whereas alpha-CnIB is present in a relatively, small amount. Chemical synthesis of alpha-CnIA was carried out using the, Fmoc methodology by selective disulfide bond formation. The biological, activity of the toxin was assessed in fish and mice. The alpha-CnIA, inhibited the fixation of iodinated alpha-bungarotoxin to Torpedo, nicotinic acetylcholine receptors with an IC50 of 0.19 microM which can be, compared to the IC50 of 0.31 microM found for the previously characterized, alpha-MI isolated from the piscivorous Conus magus. The synthetic, alpha-CnIA blocked spontaneous and evoked synaptic potentials in frog and, mouse isolated neuromuscular preparations at sub-micromolar, concentrations. Solution NMR of this toxin indicated a conformational, heterogeneity with the existence of different conformers in solution, at, slow and intermediate exchange rates relative to the NMR chemical shift, time scale, similar to that reported for alpha-GI and alpha-MI. NMR, structures were calculated for the major NMR signals representing more, than 80% of the population at 5 degrees C.

About this Structure

1B45 is a Single protein structure of sequence from Conus consors with NH2 as ligand. Full crystallographic information is available from OCA.

Reference

Biochemical characterization and nuclear magnetic resonance structure of novel alpha-conotoxins isolated from the venom of Conus consors., Favreau P, Krimm I, Le Gall F, Bobenrieth MJ, Lamthanh H, Bouet F, Servent D, Molgo J, Menez A, Letourneux Y, Lancelin JM, Biochemistry. 1999 May 11;38(19):6317-26. PMID:10320362

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