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

Journal of Hazardous Materials
Dan WuYong-Xing He

Abstract

The compound p-nitrophenol, which shows the anti-androgenic activity, can easily become anthropogenic pollutants and pose a threat to the environment and human health. Previous work indicates that the anti-androgenic mechanism of p-nitrophenol is complex and may involve several components in the AR signaling pathway, but the molecular details of how p-nitrophenol inhibits AR signaling are still not quite clear. Here, we characterized p-nitrophenol binds to the FK1 domain of an AR positive regulator FKBP51 with micromolar affinity and structural analysis of FK1 domain in complex with p-nitrophenol revealed that p-nitrophenol occupies a hydrophobic FK1 pocket that is vital for AR activity enhancement. Molecular dynamics simulation indicated that p-nitrophenol is stably bound to the FK1 pocket and the hotspot residues that involved p-nitrophenol binding are mainly hydrophobic and overlap with the AR interaction site. Furthermore, we showed that p-nitrophenol inhibits the androgen-dependent growth of human prostate cancer cells, possibly through down-regulating the expression levels of AR activated downstream genes. Taken together, our data suggests that p-nitrophenol suppresses the AR signaling pathway at least in part by blocking...Continue Reading

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Citations

Nov 23, 2019·Biochemical Society Transactions·Cristina Daneri-BecerraMario D Galigniana
Feb 6, 2019·Biomolecules·Nadia R ZgajnarMario D Galigniana
Apr 11, 2018·Acta Crystallographica. Section F, Structural Biology Communications·Jian Hong ZhaoYong Xing He

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