9W11

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

Summary for 9W11

• Entry DOI: 10.2210/pdb9w11/pdb
• Descriptor: Estrogen receptor, (3S,7S,11E)-7,14,16-trihydroxy-3-methyl-3,4,5,6,7,8,9,10-octahydro-1H-2-benzoxacyclotetradecin-1-one, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• Functional Keywords: beta-zearalenol, er-alpha, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 60402.98

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 (1.83 Å)