8R00

Crystal structure of the human PXR ligand-binding domain in complex with furanodienone

Summary for 8R00

• Entry DOI: 10.2210/pdb8r00/pdb
• Descriptor: Nuclear receptor subfamily 1 group I member 2, furanodienone (3 entities in total)
• Functional Keywords: nuclear receptor, pregnane x receptor, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 36977.77

Authors

Bourguet, W.,Carivenc, C.,Sirounian, S. (deposition date: 2023-10-30, release date: 2025-04-16)

Primary citation

Wang, X.,Zhang, G.,Bian, Z.,Chow, V.,Grimaldi, M.,Carivenc, C.,Sirounian, S.,Li, H.,Sladekova, L.,Motta, S.,Luperi, Y.,Gong, Y.,Costello, C.,Li, L.,Jachimowicz, M.,Guo, M.,Hu, S.,Wilson, D.,Balaguer, P.,Bourguet, W.,Mani, S.,Bonati, L.,Peng, H.,March, J.,Wang, H.,Wang, S.,Krause, H.M.,Liu, J.
An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.
Nat Commun, 16:1280-1280, 2025

PubMed Abstract: The literature documenting the value of drug-like molecules found in natural products is vast. Although many dietary and herbal remedies have been found to be effective for treating intestinal inflammation, the identification of their active components has lagged behind. In this study, we find that a major ginger component, furanodienone (FDN), is a selective pregnane X receptor (PXR) ligand with agonistic transcriptional outcomes. We show that FDN binds within a sub-pocket of the PXR ligand binding domain (LBD), with subsequent alterations in LBD structure. Using male mice, we show that orally provided FDN has potent PXR-dependant anti-inflammatory outcomes that are colon-specific. Increased affinity and target gene activation in the presence of synergistically acting agonists indicates further opportunities for augmenting FDN activity, efficacy and safety. Collectively, these results support the translational potential of FDN as a therapeutic agent for the treatment and prevention of colonic diseases.

PubMed: 39900639
DOI: 10.1038/s41467-025-56624-0

Experimental method

X-RAY DIFFRACTION (1.95 Å)