AB157. The environmental endocrine disruptor p-nitrophenol interacts with FKBP51, a positive regulator of androgen receptor and inhibits androgen receptor signaling in human cells
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AB157. The environmental endocrine disruptor p-nitrophenol interacts with FKBP51, a positive regulator of androgen receptor and inhibits androgen receptor signaling in human cells

Dan Wu, Zhiping Wang

Urological Surgery Institute of Lanzhou University Second Hospital, Gansu Province Urinary System Disease Research Key Laboratory, Gansu Province Urinary System Disease Clinical Medicine Center, Lanzhou 730000, China


Objective: Although it was shown that p-nitrophenol is anti-androgenic in vivo, the molecular details of how p-nitrophenol inhibits AR signaling are still not quite clear. In this report, we want to figure out this signaling in human cells.

Methods: (I) Cell viability assay; (II) endogenous expression of androgen-activated genes; (III) expression, and purification of the FK1 domain of FKBP51; (IV) fluorescence quenching assay; (V) crystallization and data collection; (VI) structure determination; (VII) molecular dynamics (MD) simulation; (VIII) the free energy calculation.

Results: we show that p-nitrophenol inhibits the androgen dependent cell growth and down-regulates the expression levels of AR target genes. Furthermore, we identified that p-nitrophenol binds with micromolar affinity to the Hsp90 co-chaperone FKBP51, a protein essential for AR activation. Crystal structure of FKBP51 in complex with p-nitrophenol revealed that p-nitrophenol occupies a hydrophobic pocket of FKBP51 that is vital for AR activity enhancement. Molecular dynamics simulation indicate that p-nitrophenol is stably bound to the FKBP51 pocket and the hotspot residues that involved p-nitrophenol binding are mainly hydrophobic and overlap with the AR interaction site.

Conclusions: our results demonstrate the anti-androgenic activity of p-nitrophenol in human cells and illustrate the binding mechanism between p-nitrophenol and its potential molecular target FKBP51, providing guidelines for assessing the long term health risks of p-nitrophenol and its derivatives.

Keywords: p-Nitrophenol; FKBP51; androgen receptor; molecular dynamics simulation


doi: 10.21037/tau.2016.s157


Cite this abstract as: Wu D, Wang Z. The environmental endocrine disruptor p-nitrophenol interacts with FKBP51, a positive regulator of androgen receptor and inhibits androgen receptor signaling in human cells. Transl Androl Urol 2016;5(Suppl 1):AB157. doi: 10.21037/tau.2016.s157

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