The evolution of farnesoid X,vitamin D,and pregnane X receptors: insights from the green-spotted pufferfish (<Emphasis Type="Italic">Tetraodon nigriviridis</Emphasis>) and other non-mammalian species |
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| Authors: | Matthew D Krasowski Ni Ai Lee R Hagey Erin M Kollitz Seth W Kullman Erica J Reschly Sean Ekins |
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| Institution: | (1) Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA;(2) Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA;(3) Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, Piscataway, NJ 08854, USA;(4) Department of Medicine, University of California - San Diego, La Jolla, CA 92093, USA;(5) Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695, USA;(6) Collaborations in Chemistry, Jenkintown, PA 19046, USA;(7) Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA |
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| Abstract: | Background The farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR) are three closely related nuclear
hormone receptors in the NR1H and 1I subfamilies that share the property of being activated by bile salts. Bile salts vary
significantly in structure across vertebrate species, suggesting that receptors binding these molecules may show adaptive
evolutionary changes in response. We have previously shown that FXRs from the sea lamprey (Petromyzon marinus) and zebrafish (Danio rerio) are activated by planar bile alcohols found in these two species. In this report, we characterize FXR, PXR, and VDR from
the green-spotted pufferfish (Tetraodon nigriviridis), an actinopterygian fish that unlike the zebrafish has a bile salt profile similar to humans. We utilize homology modelling,
docking, and pharmacophore studies to understand the structural features of the Tetraodon receptors. |
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