1yz2
Solution structure of Am2766Solution structure of Am2766
Structural highlights
FunctionO166_CONAA Delta-conotoxins bind to site 6 of voltage-gated sodium channels (Nav) and inhibit the inactivation process.[1] Publication Abstract from PubMedThe 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. Solution structure of delta-Am2766: a highly hydrophobic delta-conotoxin from Conus amadis that inhibits inactivation of neuronal voltage-gated sodium channels.,Sarma SP, Kumar GS, Sudarslal S, Iengar P, Ramasamy P, Sikdar SK, Krishnan KS, Balaram P Chem Biodivers. 2005 Apr;2(4):535-56. doi: 10.1002/cbdv.200590035. PMID:17192003[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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