Application of selenocysteine for enhancement of the reactivity of the enzymes related on redox regulation system

2014 Fiscal Year Final Research Report

• Project/Area Number: 25650040
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Tokai University
• Principal Investigator: KANAMORI Akiko 東海大学, 工学部, 教授 (00261173)
• Co-Investigator(Renkei-kenkyūsha): ITO Yukishige 理化学研究所, 伊藤細胞制御化学研究室, 主任研究員 (80168385)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: セレノシステイン / グルタチオン / フォールディング / 品質管理機構 / シャペロン / タンパク質ジスルフィドイソメラーゼ / 酸化ストレス / 酸化還元酵素

Outline of Final Research Achievements

The enzymes related on redox regulatory system work on the maintenance of the intracellular environment from reactive oxygen species (ROS) providing oxidative stress. Especially, it was reported that inactivation or decrease in chaperone activity of protein disulfide isomerase (PDI) cause accumulation of misfolded proteins resulting incidence of Alzheimer's disease. In this study, we pay attention to selenocysteine, the 21th amino acid, to introduce it into the active sites of glutathione or PDI. The difference in reactivity of cysteine and selenocysteine bring on the difference of reactivity to the molecules. We compared the effects on folding of misfolded proteins between glutathione (GSSG) and selenoglutathione (GSeSeG) by detecting the rate of recovered activity of misfolded RNase. The enhancement effect derived from GSeSeG was superior to that from GSSG on both chaperone activity of PDI and refolding of misfolded enzymes.

Free Research Field

生化学、分子生物学、細胞生物学