9F7X

Human PPARgamma ligand binding domain in complex with co-activator 1alpha peptide and bisphenol B (BPB)

9F7X の概要

• エントリーDOI: 10.2210/pdb9f7x/pdb
• 分子名称: Peroxisome proliferator-activated receptor gamma, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, bisphenol-B, ... (4 entities in total)
• 機能のキーワード: peroxisome proliferator-activated receptor gamma, bisphenol b, nuclear protein, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34722.27

構造登録者

Useini, A.,Strater, N. (登録日: 2024-05-05, 公開日: 2024-07-10)

主引用文献

Useini, A.,Schwerin, I.K.,Kunze, G.,Strater, N.
Structural Studies on the Binding Mode of Bisphenols to PPAR gamma.
Biomolecules, 14:-, 2024

PubMed Abstract: Bisphenol A (BPA) and bisphenol B (BPB) are widely used in the production of plastics, and their potential adverse health effects, particularly on endocrine disruption and metabolic health, have raised concern. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a pivotal role in metabolic regulation and adipogenesis, making it a target of interest in understanding the development of obesity and associated health impacts. In this study, we employ X-ray crystallography and molecular dynamics (MD) simulations to study the interaction of PPARγ with BPA and BPB. Crystallographic structures reveal the binding of BPA and BPB to the ligand binding domain of PPARγ, next to C285, where binding of partial agonists as well as antagonists and inverse agonists of PPARγ signaling has been previously observed. However, no interaction of BPA and BPB with Y437 in the activation function 2 site is observed, showing that these ligands cannot stabilize the active conformation of helix 12 directly. Furthermore, free energy analyses of the MD simulations revealed that I341 has a large energetic contribution to the BPA and BPB binding modes characterized in this study.

PubMed: 38927044
DOI: 10.3390/biom14060640

実験手法

X-RAY DIFFRACTION (1.63 Å)