ERRgamma tethers strongly bisphenol A and 4-alpha-cumylphenol in an induced-fit manner

Biochem Biophys Res Commun. 2008 Aug 29;373(3):408-13. doi: 10.1016/j.bbrc.2008.06.050. Epub 2008 Jun 26.


A receptor-binding assay and X-ray crystal structure analysis demonstrated that the endocrine disruptor bisphenol A (BPA) strongly binds to human estrogen-related receptor gamma (ERRgamma). BPA is well anchored to the ligand-binding pocket, forming hydrogen bonds with its two phenol-hydroxyl groups. In this study, we found that 4-alpha-cumylphenol lacking one of its phenol-hydroxyl groups also binds to ERRgamma very strongly. The 2.0 A crystal structure of the 4-alpha-cumylphenol/ERRgamma complex clearly revealed that ERRgamma's Leu345-beta-isopropyl plays a role in the tight binding of 4-alpha-cumylphenol and BPA, rotating in a back-and-forth induced-fit manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds
  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • Hydrogen Bonding
  • Leucine / chemistry
  • Ligands
  • Phenols / chemistry
  • Phenols / metabolism*
  • Protein Conformation
  • Receptors, Estrogen / chemistry
  • Receptors, Estrogen / metabolism*


  • Benzhydryl Compounds
  • ESRRG protein, human
  • Ligands
  • Phenols
  • Receptors, Estrogen
  • 4-cumylphenol
  • Leucine
  • bisphenol A

Associated data

  • PDB/2ZAS
  • PDB/2ZBS