ヨコヤマ ケン   YOKOYAMA KEN
  横山 謙
   所属   京都産業大学  生命科学部 先端生命科学科
   職種   教授
言語種別 英語
発行・発表の年月 2009/02
形態種別 研究論文
査読 査読あり
標題 Mechanism of Inhibition of the V-Type Molecular Motor by Tributyltin Chloride
執筆形態 その他
掲載誌名 BIOPHYSICAL JOURNAL
出版社・発行元 CELL PRESS
巻・号・頁 96(3),pp.1210-1217
著者・共著者 Mizuho Takeda,Chip Suno-Ikeda,Katsuya Shimabukuro,Masasuke Yoshida,Ken Yokoyama
概要 Tributyltin chloride (TBT-Cl) is an endocrine disruptor found in many animal species, and it is also known to bean inhibitor for the V-ATPases that are emerging as potential targets in the treatment of diseases such as osteoporosis and cancer. We demonstrated by using biochemical and single-molecular imaging techniques that TBT-Cl arrests an elementary step for rotary catalysis of the V(1) motor domain. In the presence of TBT-Cl, the consecutive rotation of V(1) paused for a long duration (similar to 0.5 s), even at saturated ATIP concentrations, and the pausing positions were localized at 120 degrees intervals. Analysis of both the pausing time and moving time revealed that TBT-Cl has little effect on the binding affinity for ATP, but, rather, it arrests the catalytic event(s). This is the first report to demonstrate that an inhibitor arrests an elementary step for rotary catalysis of a V-type ATIP-driven rotary motor.
DOI 10.1016/j.bpj.2008.10.031
ISSN 0006-3495
PMID 19186155