ミヤノ マサシ   MIYANO, Masashi
  宮野 雅司
   所属   青山学院大学  理工学部 化学・生命科学科
   職種   教授
言語種別 英語
発行・発表の年月 2018/03
形態種別 学術雑誌
査読 査読有り
標題 Na+-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1
執筆形態 共同
掲載誌名 Nature Chemical Biology
掲載区分国外
出版社・発行元 Springer Nature
巻・号・頁 14(3),pp.262-269
著者・共著者 Tetsuya Hori, Toshiaki Okuno, Knio Hirata, Keitaro Yamashita, Yoshiaki Kawano, Masaki Yamamoto, Masakatsu Hato, Motonao Nakamura, Takao Shimizu, Takehiko Yokomizo, Masashi Miyano & Shigeyuki Yokoyama
概要 Most G-protein-coupled receptors (GPCRs) are stabilized in common in the inactive state by the formation of the sodium ion–centered water cluster. We determined the crystal structure of the leukotriene B4 (LTB4) receptor BLT1 bound with BIIL260, a chemical bearing a benzamidine moiety. The amidine group occupies the sodium ion and water locations, and mimics the entire sodium ion–centered water cluster. Thus, BLT1 is fixed in the inactive state, and the transmembrane helices cannot change their conformations to form the active state, and the benzamidine molecule alone serves as a negative allosteric modulator for BLT1. The structure will enable the rational development of inverse agonists specific for each GPCR.
DOI 10.1038/nchembio.2547