Investigation of the reaction mechanism of orotidine monophosphate decarboxylase using the distortion of the substrate

• Project/Area Number: 22770102
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Structural biochemistry
• Research Institution: Kyoto University
• Principal Investigator: FUJIHASHI Masahiro 京都大学, 大学院・理学研究科, 助教 (10397581)
• Co-Investigator(Renkei-kenkyūsha): ISHIDA Toyokazu 産業技術総合研究所, 計算科学, 研究員 (70443166)
• Research Collaborator: KOTRA P. lakshmi トロント総合研究所
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: X線結晶解析 / ODCase / 反応中間体構造 / 基質構造の歪み / 酵素反応機構 / 蛋白質X線結晶構造解析 / 酵素基質複合体 / OMPDC / OMPDCase / タンパク質X線結晶構造解析

Research Abstract

Orotidine 5'-monophosphate decarboxylase(ODCase) accelerates the decarboxylation of orotidine 5'-monophosphate(OMP) to uridine 5'-monophosphate(UMP) by 17 orders of magnitude. We have determined several crystal structures with ligand analogues and performed computer simulations of the enzyme's short-lived intermediates. The results show that ODCase catalyzes the decarboxylation reaction utilizing both ground state destabilization and transition state stabilization.

Research Products

• [Presentation] オロチジン一リン酸脱炭酸酵素の反応における基質の歪みの役割 (2011)
  • Author(s): 藤橋雅宏, 石田豊和, 黒田新悟, Emil F Pai, Lakshmi P Kotra, 三木邦夫
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: ホテル阪急エキスポパーク(大阪府)
  • Year and Date: 2011-06-08
• [Presentation] オロチジンーリン酸脱炭酸酵素の反応における基質の歪みの役割 (2011)
  • Author(s): 藤橋雅宏, 石田豊和, 黒田新悟, Emil F Pai, Lakshmi P Kotra, 三木邦夫
  • Organizer: 第11回日本蛋白質科学会年会
  • Place of Presentation: ホテル阪急エキスポパーク(大阪府)
  • Year and Date: 2011-06-08