Elucidation of the molecular basis for de novo phosphatidic acid synthesis through enzymological studies

Research Project

Project/Area Number	17K15259
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Applied biochemistry
Research Institution	Kyoto University
Principal Investigator	OGAWA Takuya 京都大学, 化学研究所, 助教 (40756318)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000) Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	アシルグリセロールリン酸アシル基転移酵素 / グリセロリン脂質 / 脂質代謝 / リン脂質 / 細胞膜組成 / 阻害剤開発 / PlsC / 変異解析 / アシル基転移酵素 / 膜タンパク質
Outline of Final Research Achievements	I here attempted to analyze the function and reaction mechanism of acylglycerophosphate acyltransferase (AGPAT), which is involved in the membrane phospholipid synthesis. Although it is the primary enzyme required for the formation of cellular membrane, the knowledge of its enzymological properties has been limited so far because it is a membrane protein that often lose its activity during purification and thus is difficult to assay. In this study, I developed an AGPAT inhibitor that may be suitable for structural analysis and identified and functionally analyzed several AGPATs that have different substrate selectivity.
Academic Significance and Societal Importance of the Research Achievements	細胞膜の脂肪酸組成は各細胞が正常に働くために、また細胞外の環境変化に順応するために適切に調節されている。AGPATは細胞膜の脂肪酸組成を規定する要因の１つであるが、これまで個々のAGPATの反応特性や作用機序に関する知見は乏しかった。本研究における発見は、AGPATの酵素機能とその多様性について新しい知見を与えるとともに、細胞膜脂質の多様性創出とその生理的意義の理解に向けて基盤となる成果だと考えられる。