1B45

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

Summary for 1B45

• Entry DOI: 10.2210/pdb1b45/pdb
• Descriptor: ALPHA-CNIA (1 entity in total)
• Functional Keywords: alpha-conotoxin, conus consors, nicotinic acetylcholine receptor, toxin
• Biological source: Conus consors
• Total number of polymer chains: 1
• Total formula weight: 1548.84

Authors

Favreau, P.,Krimm, I.,Le Gall, F.,Bobenrieth, M.J.,Lamthanh, H.,Bouet, F.,Servent, D.,Molgo, J.,Menez, A.,Letourneux, Y.,Lancelin, J.M. (deposition date: 1999-01-05, release date: 1999-07-09, Last modification date: 2024-10-09)

Primary citation

Favreau, P.,Krimm, I.,Le Gall, F.,Bobenrieth, M.J.,Lamthanh, H.,Bouet, F.,Servent, D.,Molgo, J.,Menez, A.,Letourneux, Y.,Lancelin, J.M.
Biochemical characterization and nuclear magnetic resonance structure of novel alpha-conotoxins isolated from the venom of Conus consors.
Biochemistry, 38:6317-6326, 1999

PubMed Abstract: 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.

PubMed: 10320362
DOI: 10.1021/bi982817z

Experimental method

SOLUTION NMR