ERR-beta

February 2021

Estrogen-related receptor β (ERRβ) is an orphan nuclear receptor that, together with ERR α and γ, constitutes the ERR family. ERR ß is found in many tissues in the human body, such as the heart, kidney, prostate, central nervous system, placenta, etc. A growing number of studies indicate a tumor-suppressive role of ERR β in human malignancies and its potential as a therapeutic target.

Nevertheless, ERR β ligand-binding domain (LBD) is the last resolved and, therefore, the least explored and the less characterized structure among the entire ERR family.

To determine its ligand selectivity, you can compare the recently resolved X-Ray of ERR β with other ERR subtype structures using 3decision Sequence Explorer. There you can manually search and browse through the collection of all existing ERR α and ERR γ PDB structures and get an overview of each target’s pocket-lining residues and protein-ligand interactions mapped onto the canonical sequence. You can directly combine the sequence knowledge with the three-dimensional structural information on the 3D Viewer.

Once you superpose the chosen structures, you can turn on the pocket Highlight Mode to quickly spot binding site differences and study key interactions of co-crystallized ligands. This way, 3decision can help you explore strategies for designing selective compounds targeting each ERR individually.

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3decision Sequence Explorer allows you to combine Sequence Explorer with the 3D structural information to study ligand selectivity of ERR β LBD (PDB: 6LIT).

Reference: Yao B, Zhang S, Wei Y, Tian S, Lu Z, Jin L, He Y, Xie W, Li Y. Structural Insights into the Specificity of Ligand Binding and Coactivator Assembly by Estrogen-Related Receptor β. J Mol Biol. 2020 Sep 4;432(19):5460-5472. doi: 10.1016/j.jmb.2020.08.007. Epub 2020 Aug 12. PMID: 32795533. https://pubmed.ncbi.nlm.nih.gov/32795533/