Theoretical elucidation on the full reaction mechanisms of threonine synthase

2016 Fiscal Year Final Research Report

• Project/Area Number: 26410002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical chemistry
• Research Institution: University of Tsukuba
• Principal Investigator: SHOJI MITSUO 筑波大学, 計算科学研究センター, 助教 (00593550)
• Co-Investigator(Renkei-kenkyūsha): HAYASHI HIDEYUKI 大阪医科大学, 医学部, 教授 (00183913)
• Research Collaborator: UJIIE YUZURU 筑波大学, 数理物質系 ; TANAKA WATARU 筑波大学, 数理物質系
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: トレオニン合成酵素 / 反応機構 / 生成物支援機構 / QM/MM / molecular dynamics / 自由エネルギー / スパコン / 反応制御

Outline of Final Research Achievements

Reaction mechanisms of the threonine synthase (ThrS) were theoretically investigated by using the mixed quantum mechanics/molecular mechanics (QM/MM) and classical molecular dynamics methods. By utilizing the supercomputers, long time scale CMD (total 3 micro sec) were performed and important protein-substrate interactions and free energy changes were elucidated. Significantly, conformational changes on the active site molecules (PLP, water and amino acid residues) were observed depending on the intermediate states. It was also shown that the anion important for the product assisted mechanism plays important role to construct active site conformations. These results clearly indicate that precise structural controls optimized for the reactions are performed in ThrS. This reaction control mechanism provides valuable insights for other reaction mechanisms and functional modifications.

Free Research Field

量子化学