Abstract

The estrogen receptor (ER) is a member of the nuclear receptor superfamily and has two subtypes: ERα and ERβ. Inhibition of ERα is an effective therapeutic strategy in breast cancer. In contrast, ERβ is the presumed drug target of various autoimmune diseases. Many experimental structures of ERα/β have been reported; however, their structures vary due to ligand variability. Here, we performed structural bioinformatics studies for three-dimensional structures of ERs retrieved from the protein data bank (PDB) and clarify the detailed structural differences between ERα and ERβ. In total, 48 structures registered in the PDB were analyzed by HBOP and HBSITE, which we developed to identify ligand-binding cavities in proteins. PDB entries were clustered by number, shape, size, and location of the ligand-binding pockets. In addition, C-terminal domain shapes, which are divided into “agonist form” and “antagonist form,” were also used for clustering. We classified 27 entries of ERα into five clusters and 21 entries of ERβ into seven clusters (a total of 12 clusters). Differences in the pockets and hydrogen bonds with ligands were observed between ERα and ERβ and occurred even within the same ER species. Therefore, we conclude that the structure of ERs is diverse and is affected by ligands.

Details

Title
Structural differences between the ligand-binding pockets of estrogen receptors alpha and beta
Author
Kato, K 1 ; Fujii, K 2 ; Nakayoshi, T 2 ; Watanabe, Y 3 ; Fukuyoshi, S 2 ; Ohta, K 4 ; Endo, Y 4 ; Yamaotsu, N 5 ; Hirono, S 5 ; Kurimoto, E 6 ; Oda, A 7 

 Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi 468-8503, Japan; Department of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan 
 Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan 
 Faculty of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan 
 Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi 981-8558, Japan 
 School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan 
 Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi 468-8503, Japan 
 Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, Aichi 468-8503, Japan; Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan 
Publication year
2018
Publication date
Dec 2018
Publisher
IOP Publishing
ISSN
17426588
e-ISSN
17426596
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2565412803
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.