Identification of Palytoxin-Ca2+ Complex by NMR and Molecular Modeling Techniques

More than 40 years after its isolation, the understanding of how palytoxin interacts with biological systems has yet to be fully determined. The Na+,K+-ATPase pump constitutes a molecular receptor for palytoxin that is able to convert the pump into an open channel, with consequent loss of cellular K+ and remarkable rise of cytosolic Na+ levels. In addition, a slight permeability to Ca2+ is detected when palytoxin binds to the pump. It has been demonstrated that the increase of cytosolic free Ca2+ concentration gives rise to downstream events ultimately leading to cell death. The widely accepted recognition of the dependence of important cellular events on calcium ion concentration propelled us to investigate the occurrence of palytoxin-Ca2+ complex in aqueous solution by NMR- and molecular modeling-based approach. We identified two specific regions of palytoxin where Ca2+ is preferentially coordinated. This study constitutes the first characterization of a calcium complex with palytoxin and, as such, is expected to support the investigation of the toxin molecular bioactivity.