Solution Structure of δ-Am2766: A Highly Hydrophobic δ-Conotoxin from Conus amadis That Inhibits Inactivation of Neuronal Voltage-Gated Sodium Channels
Article first published online: 18 APR 2005
Copyright © 2005 Verlag Helvetica Chimica Acta AG, Zürich
Chemistry & Biodiversity
Volume 2, Issue 4, pages 535–556, April 2005
How to Cite
Sarma, Siddhartha P., Kumar, G. Senthil., Sudarslal, S., Iengar, P., Ramasamy, P., Sikdar, Sujit K., Krishnan, K. S. and Balaram, P. (2005), Solution Structure of δ-Am2766: A Highly Hydrophobic δ-Conotoxin from Conus amadis That Inhibits Inactivation of Neuronal Voltage-Gated Sodium Channels. Chemistry & Biodiversity, 2: 535–556. doi: 10.1002/cbdv.200590035
- Issue published online: 18 APR 2005
- Article first published online: 18 APR 2005
- Manuscript Received: 8 OCT 2004
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.