9W12

Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with ZOL-P

This is a non-PDB format compatible entry.

Summary for 9W12

• Entry DOI: 10.2210/pdb9w12/pdb
• Descriptor: Estrogen receptor, (4S,8S,11S,12E)-4-methyl-8,11,16,18-tetrakis(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),12,15,17-tetraen-2-one, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• Functional Keywords: er-alpha, zol-p, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 60525.12

Authors

Peng, R.M.,Min, J.,Li, K.K. (deposition date: 2025-07-25, release date: 2026-03-18, Last modification date: 2026-09-30)

Primary citation

Liu, Z.,Peng, R.,Li, Q.,Chen, C.C.,Xin, L.,Li, K.,Huang, J.W.,Liu, X.,Zhang, X.,Hu, L.,Luo, S.,Zhou, H.,Li, A.,Min, J.,Guo, R.T.
A distinct zearalenone detoxification strategy mediated by cytochrome P450.
Food Chem, 510:148697-148697, 2026

PubMed Abstract: Developing the bio-detoxification of estrogenic mycotoxin zearalenone (ZEN) and its more potent metabolite α-zearalenol (α-ZOL) represents a research priority in food safety. Here, we report a variant cytochrome P450 enzyme termed T8F3 that consumes 54% ZEN and 63.9% α-ZOL in an initial screening assay. The hydroxylated products of ZEN and α-ZOL, termed ZEN-P and ZOL-P, respectively, were isolated, purified and structurally characterized. The estrogenicity of ZEN-P and ZOL-P is suppressed by 21- and 105-fold, respectively, compared with their parental compounds. Structural elucidation shows that T8F3-catalyzed hydroxylation at β-C8' (ZEN) and α-C3' (α-ZOL) positions, which might introduce steric hinderance that compromises the binding to estrogen receptor α, establishing a structure-detoxification relationship. Altogether, our study reports the first P450-mediated hydroxylation of ZEN and α-ZOL, resolves the mechanism of detoxification and addresses the behaviors of the hydroxylated ZEN and α-ZOL. These results should offer novel bio-detoxification machineries toward ZEN and derivatives.

PubMed: 41795529
DOI: 10.1016/j.foodchem.2026.148697

Experimental method

X-RAY DIFFRACTION (1.75 Å)