学術雑誌論文

学術雑誌論文

text

Scientific Reports. 2014, 5, p. 8520

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

Nature Research

英語

text

2014-02-17

https://doi.org/10.1038/srep08520

Harada, S., Hiromori, Y., Nakamura, S. et al. Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds. Sci Rep 5, 8520 (2015). https://doi.org/10.1038/srep08520.

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT.

© 2015 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.

79034

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

Nature Research

英語

2014-02-17

Scientific Reports

5

8520

https://doi.org/10.1038/srep08520

25687586

https://hdl.handle.net/11094/79034