Reaction mechanism analysis and inhibitor screening of helminthic fumarate quinone reductase

• Project/Area Number: 26460504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Hirosaki University
• Principal Investigator: SAKAMOTO Kimitoshi 弘前大学, 農学生命科学部, 准教授 (50361465)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 蠕虫 / ミトコンドリア / コハク酸脱水素酵素 / ロドキノン / ミトコンドリア呼吸鎖

Outline of Final Research Achievements

Echinococcus mitochondrial respiratory complexII contain unusual amino acid at very conserved site, which was Phe instead of common Ala. Same substitution was also found in bacteria Rhodospirillum rubrum. To asses the influence of this amino acid on catalysis, mutaion Ala to Phe and Phe to Ala was introduced into the complex II of Rhodobacter capsulatus and R. rubrum, respectively.
As a result, this mutation read to enhancement of Quinol-Fumarate reductase activities and not much change in Succinate-Quinone reductase activities. This amino acid has some roll on activity adjustment.

Research Products

• [Int'l Joint Research] ペンシルバニア大学(米国)
• [Journal Article] The Open Form Inducer Approach for Structure-Based Drug Design (2016)
  • Author(s): D. K. Inaoka, M. Iida, T. Tabuchi, T. Honma, N. Lee, S. Hashimoto, S. Matsuoka, T. Kuranaga, K. Sato, T. Shiba, K. Sakamoto, E. O. Balogun, S. Suzuki, T. Nara, J. R. Rocha, C. A. Montanari, A. Tanaka, M. Inoue, K. Kita, S. Harada
  • Journal Title: PLoS ONE Volume: 11 Issue: 11 Pages: e0167078-e0167078
  • DOI: 10.1371/journal.pone.0167078
  • NAID: 120006987593
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Knockdown of the coenzyme Q synthesis gene Smed-dlp1 affects planarian regeneration and tissue homeostasis (2015)
  • Author(s): Shiobara Y, Harada C, Shiota T, Sakamoto K, Kita K, Tanaka S, Tabata K, Sekie K, Yamamoto Y, Sugiyama T
  • Journal Title: Redox Biol Volume: 6 Pages: 599-606
  • DOI: 10.1016/j.redox.2015.10.004
  • Peer Reviewed / Open Access
• [Journal Article] Enhancement of protocatechuate decarboxylase activity for the effective production of muconate from lignin-related aromatic compounds. (2014)
  • Author(s): Sonoki T., Morooka M., Sakamoto K., Otsuka Y., Nakamura M, Jellison J, Goodell B.
  • Journal Title: Journal of Biotechnology Volume: 192 Pages: 71-77
  • DOI: 10.1016/j.jbiotec.2014.10.027
  • Peer Reviewed
• [Presentation] ユビキノンおよびロドキノンの機能研究材料としてのプラナリア (2016)
  • Author(s): 鎌田紗綾, 坂元君年
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 東北大学
  • Year and Date: 2016-09-25
• [Presentation] Rhodobacter capsulatus由来bdキノール酸化酵素の解析 (2016)
  • Author(s): 坂元君年, 佐々木智子, Fevzi Daldal
  • Organizer: 日本生化学会東北支部第82回例会
  • Place of Presentation: 弘前大学
  • Year and Date: 2016-05-21
• [Presentation] アルファプロテオバクテリア綱の細菌が持つコハク酸脱水素酵素の鉄硫黄クラスター近傍アミノ酸変異による活性制御の解析 (2016)
  • Author(s): 前田晴香、Fevzi Daldal、坂元君年
  • Organizer: 日本農芸化学会2016年大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-27
• [Presentation] 淡水性プラナリアからのミトコンドリア単離 (2014)
  • Author(s): 室川聡大、櫻田拓也、坂元君年
  • Organizer: 第87回生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18