Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR

Hao Li, Matthew R. Redinbo, Madhukumar Venkatesh, Sean Ekins, Anik Chaudhry, Nicolin Bloch, Abdissa Negassa, Paromita Mukherjee, Ganjam V. Kalpana, Sridhar Mani

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Ketoconazole binds to and antagonizes pregnane X receptor (PXR) activation. Results: Yeast high throughput screens of PXR mutants define a unique region for ketoconazole binding. Conclusion: Ketoconazole genetically interacts with specific PXR surface residues. Significance: A yeast-based genetic method to discover novel nuclear receptor interactions with ligands that associate with surface binding sites is suggested.

Original languageEnglish (US)
Pages (from-to)13655-13668
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number19
DOIs
StatePublished - May 10 2013

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Ketoconazole
Xenobiotics
Cytoplasmic and Nuclear Receptors
Yeast
Yeasts
Chemical activation
Binding Sites
Throughput
Ligands
pregnane X receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR. / Li, Hao; Redinbo, Matthew R.; Venkatesh, Madhukumar; Ekins, Sean; Chaudhry, Anik; Bloch, Nicolin; Negassa, Abdissa; Mukherjee, Paromita; Kalpana, Ganjam V.; Mani, Sridhar.

In: Journal of Biological Chemistry, Vol. 288, No. 19, 10.05.2013, p. 13655-13668.

Research output: Contribution to journalArticle

Li, Hao ; Redinbo, Matthew R. ; Venkatesh, Madhukumar ; Ekins, Sean ; Chaudhry, Anik ; Bloch, Nicolin ; Negassa, Abdissa ; Mukherjee, Paromita ; Kalpana, Ganjam V. ; Mani, Sridhar. / Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 19. pp. 13655-13668.
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