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Solution structure of $\delta$-Am2766: A highly hydrophobic $ \delta$-conotoxin from Conus amadis that inhibits inactivation of neuronal voltage-gated sodium channels

Sarma, Siddhartha P and Kumar, G Senthil and Sudarslal, S and Iengar, Prathima and Ramasamy, P and Sikdar, Sujit K and Krishnan, KS and Balaram, Padmanabhan (2005) Solution structure of $\delta$-Am2766: A highly hydrophobic $ \delta$-conotoxin from Conus amadis that inhibits inactivation of neuronal voltage-gated sodium channels. In: Chemistry & Biodiversity, 2 (4). pp. 535-556.

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The three-dimensional (3D) NMR solution structure (MeOH) of the highly hydrophobic delta-conotoxin delta-Am2766 from the molluscivorous snail Conus amadis has been determined. Fifteen converged structures were obtained on the basis of 262 distance constraints, 25 torsion-angle constraints, and ten constraints based on disulfide linkages and H-bonds. The root-mean-square deviations (rmsd) about the averaged coordinates of the backbone (N, C(alpha), C) and (all) heavy atoms were 0.62+/-0.20 and 1.12+/-0.23 A, respectively. The structures determined are of good stereochemical quality, as evidenced by the high percentage (100%) of backbone dihedral angles that occupy favorable and additionally allowed regions of the Ramachandran map. The structure of delta-Am2766 consists of a triple-stranded antiparallel beta-sheet, and of four turns. The three disulfides form the classical 'inhibitory cysteine knot' motif. So far, only one tertiary structure of a delta-conotoxin has been reported; thus, the tertiary structure of delta-Am2766 is the second such example. Another Conus peptide, Am2735 from C. amadis, has also been purified and sequenced. Am2735 shares 96% sequence identity with delta-Am2766. Unlike delta-Am2766, Am2735 does not inhibit the fast inactivation of Na+ currents in rat brain Na(v)1.2 Na+ channels at concentrations up to 200 nM.

Item Type: Journal Article
Publication: Chemistry & Biodiversity
Publisher: John Wiley and Sons
Additional Information: Copyright of this article belongs to John Wiley and Sons.
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 08 Jan 2010 06:43
Last Modified: 19 Sep 2010 04:56
URI: http://eprints.iisc.ac.in/id/eprint/17354

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