CgNa, a type I toxin from the giant Caribbean sea anemone Condylactis gigantea shows structural similarities to both type I and II toxins, as well as distinctive structural and functional properties 1

CgNa (Condylactis gigantea neurotoxin) is a 47-amino-acidresidue toxin from the giant Caribbean sea anemone Condylactis gigantea. The structure of CgNa, which was solved by 1 HNMR spectroscopy, is somewhat atypical and displays significant homology with both type I and II anemone toxins. CgNa also displays a considerable number of exceptions to the canonical structural elements that are thought to be essential for the activity of this group of toxins. Furthermore, unique residues in CgNa define a characteristic structure with strong negatively charged surface patches. These patches disrupt a surface-exposed cluster of hydrophobic residues present in all anemone-derived toxins described to date. A thorough characterization by patch‐clamp analysis using rat DRG (dorsal root ganglion) neurons indicated that CgNa preferentially binds to TTX-S (tetrodotoxinsensitive) voltage-gated sodium channels in the resting state. This association increased the inactivation time constant and the rate of recovery from inactivation, inducing a significant shift in the steadystateofinactivationcurvetotheleft.Thespecificstructural featuresofCgNamayexplainitsweakerinhibitorycapacitywhen compared with the other type I and II anemone toxins.