Solution structure of Am2766: A highly hydrophobic d-conotoxin from Conus amadis that inhibits inactivation of brain voltage gated sodium channels

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

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Abstract

The three-dimensional (3D) NMR solution structure (MeOH) of the highly hydrophobic δ-conotoxin δ-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, Cα, C) and (all) heavy atoms were 0.62±0.20 and 1.12±0.23 Å, 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 δ-Am2766 consists of a triple-stranded antiparallel β-sheet, and of four turns. The three disulfides form the classical ‘inhibitory cysteine knot’ motif. So far, only one tertiary structure of a δ-conotoxin has been reported; thus, the tertiary structure of δ-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 δ-Am2766. Unlike δ-Am2766, Am2735 does not inhibit the fast inactivation of Na+ currents in rat brain Nav1.2 Na+ channels at concentrations up to 200 nM.

Item Type:	Journal Article
Publication:	Chemistry & Biodiversity
Publisher:	Verlag Helvetica Chimica Acta
Additional Information:	Copyright of this article belongs to Verlag Helvetica Chimica Acta.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	25 Feb 2011 06:21
Last Modified:	12 Jul 2013 12:25
URI:	http://eprints.iisc.ac.in/id/eprint/33892

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