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 Kalpana; Sridhar Mani

doi:10.1074/jbc.M113.455485

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 Kalpana, Sridhar Mani

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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 language	English (US)
Pages (from-to)	13655-13668
Number of pages	14
Journal	Journal of Biological Chemistry
Volume	288
Issue number	19
DOIs	https://doi.org/10.1074/jbc.M113.455485
State	Published - May 10 2013
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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title = "Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR",

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.",

author = "Hao Li and Redinbo, {Matthew R.} and Madhukumar Venkatesh and Sean Ekins and Anik Chaudhry and Nicolin Bloch and Abdissa Negassa and Paromita Mukherjee and Ganjam Kalpana and Sridhar Mani",

year = "2013",

month = may,

day = "10",

doi = "10.1074/jbc.M113.455485",

language = "English (US)",

volume = "288",

pages = "13655--13668",

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T1 - Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR

AU - Li, Hao

AU - Redinbo, Matthew R.

AU - Venkatesh, Madhukumar

AU - Ekins, Sean

AU - Chaudhry, Anik

AU - Bloch, Nicolin

AU - Negassa, Abdissa

AU - Mukherjee, Paromita

AU - Kalpana, Ganjam

AU - Mani, Sridhar

PY - 2013/5/10

Y1 - 2013/5/10

N2 - 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.

AB - 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.

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EP - 13668

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 19

ER -

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

Abstract

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