2B1Z

Human estrogen receptor alpha ligand-binding domain in complex with 17methyl-17alpha-dihydroequilenin and a glucoc interacting protein 1 NR box II peptide

Summary for 2B1Z

• Entry DOI: 10.2210/pdb2b1z/pdb
• Related: 2B1V 2B23
• Descriptor: Estrogen receptor, Nuclear receptor coactivator 2, 17-METHYL-17-ALPHA-DIHYDROEQUILENIN, ... (4 entities in total)
• Functional Keywords: estrogen receptor, lbd, grip peptide, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 62780.26

Authors

Rajan, S.S.,Hsieh, R.W.,Sharma, S.K.,Greene, G.L. (deposition date: 2005-09-16, release date: 2006-09-19, Last modification date: 2024-10-16)

Primary citation

Hsieh, R.W.,Rajan, S.S.,Sharma, S.K.,Greene, G.L.
Molecular characterization of a B-ring unsaturated estrogen: implications for conjugated equine estrogen components of premarin.
Steroids, 73:59-68, 2008

PubMed Abstract: Conjugated equine estrogens (CEEs) are routinely used for hormone replacement therapy (HRT), making it important to understand the activities of individual estrogenic components. Although 17beta-estradiol (17beta-E2), the most potent estrogen in CEE, has been extensively characterized, the actions of nine additional less potent estrogens are not well understood. Structural differences between CEEs and 17beta-E2 result in altered interactions with the two estrogen receptors (ERalpha and ERbeta) and different biological activities. To better understand these interactions, we have determined the crystal structure of the CEE analog, 17beta-methyl-17alpha-dihydroequilenin (NCI 122), in complex with the ERalpha ligand-binding domain and a peptide from the glucocorticoid receptor-interacting protein 1 (GRIP1) coactivator. NCI 122 has chemical properties, including an unsaturated B-ring and 17alpha-hydroxyl group, which are shared with some of the estrogens found in CEEs. Structural analysis of the NCI 122-ERalpha LBD-GRIP1 complex, combined with biochemical and cell-based comparisons of CEE components, suggests that factors such as decreased ligand flexibility, decreased ligand hydrophobicity and loss of a hydrogen bond between the 17-hydroxyl group and His524, contribute significantly to the reduced potency of CEEs on ERalpha.

PubMed: 17949766
DOI: 10.1016/j.steroids.2007.08.014

Experimental method

X-RAY DIFFRACTION (1.78 Å)