Activation of a tunicate (Ciona intestinalis) xenobiotic receptor orthologue by both natural toxins and synthetic toxicants

  • Andrew E. Fidler, Patrick T. Holland, Erica J. Reschly, Sean Ekins, Matthew D. Krasowski
  • Toxicon, February 2012, Elsevier
  • DOI: 10.1016/j.toxicon.2011.12.008

Activation of CiVDR/PXR

What is it about?

We examined ligand binding by a xenobiotic receptor ortholog (VDR/PXR) of the tunicate Ciona intestinalis. Natural and synthetic toxins were assessed for binding to this receptor in vitro. Natural toxins may have acted as selected agents in the molecular evolution of the xenobiotic receptor.

Why is it important?

Pharmacophores were generated using the ligands and biologiocal data generated for the CiVDR/PXR. The common feature models suggested 2 hydrophobic features and a hydrogen bond acceptor were common features in the activiators. This pharmacophore had been previously generated for 3 earlier described ligands. The suggestion is that adaptive evolution has occured to the toxins okadaic acid and pectenotoxin-2.

Perspectives

Dr Sean Ekins
Collaborations in Chemistry

This xenobiotic receptor has narrower ligand selectivity to human and other PXRs. Tunicate xenobiotic receptor molecular evolution may yield insights into the role of xenobiotics in marine ecology and evolution of nuclear receptors.

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http://dx.doi.org/10.1016/j.toxicon.2011.12.008

The following have contributed to this page: Dr Sean Ekins