Post-translational modification of reactive sulfur species producing enzymes

• Project/Area Number: 15K18994
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: Tsuchiya Yukihiro 昭和薬科大学, 薬学部, 講師 (30455406)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 活性イオウ分子 / 翻訳後修飾 / リン酸化修飾

Outline of Final Research Achievements

We investigated post-translational modification of reactive sulfur species producing enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE).
We found that the serine-mutated CBS has no activity. Therefore, phosphorylation of the serine residue is crucial for its activity. Treatment of CSE with NO donor decreased its activity, and treatment with reactive sulfur species donor decreased its activity. These data indicate that CBS and CSE might be controlled by its post-translational modification.

Research Products

• [Journal Article] 1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides (2017)
  • Author(s): Abiko Y, Sha L, Shinkai Y, Unoki T, Luong NC, Tsuchiya Y, Watanabe Y, Hirose R, Akaike T, Kumagai Y.
  • Journal Title: Free Radic Biol Med Volume: 104 Pages: 118-128
  • DOI: 10.1016/j.freeradbiomed.2016.12.047
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide (2017)
  • Author(s): K. Hanaoka, K. Sasakura, Y. Suwanai, S. Toma-Fukai, K. Shimamoto, Y. Takano, N. Shibuya, T. Terai, T. Komatsu, T. Ueno, Y. Ogasawara, Y. Tsuchiya, Y. Watanabe, H. Kimura, C. Wang, M. Uchiyama, H. Kojima, T. Okabe, Y. Urano, T. Shimizu, T. Nagano
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 40227-40227
  • DOI: 10.1038/srep40227
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Formation of Sulfur Adducts of N-Acetyl-p-benzoquinoneimine, an Electrophilic Metabolite of Acetaminophen in Vivo: Participation of Reactive Persulfides. (2015)
  • Author(s): Abiko Y., Ishii I., Kamata S., Tsuchiya Y., Watanabe Y., Ihara H., Akaike T., Kumagai Y.
  • Journal Title: Chem. Res. Toxicol. Volume: 28 Issue: 9 Pages: 1796-1802
  • DOI: 10.1021/acs.chemrestox.5b00245
  • Peer Reviewed / Open Access
• [Presentation] 活性イオウ分子種の新しい解析法の構築 (2016)
  • Author(s): Abdul Hamid Hisyam、井田智章、笠松真吾、居原秀、土屋幸弘、渡邊泰男、澤智裕、藤井重元、赤池孝章
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台国際センター・東北大学川内北キャンパス（宮城県・仙台市）
  • Year and Date: 2016-09-25
• [Presentation] Development of a new detection system of reactive sulfur species (2016)
  • Author(s): Hisyam Abdul Hamid, Tomoaki Ida, Shingo Kasamatsu, Hideshi Ihara, Yukihiro Tsuchiya, Yasuo Watanabe, Tomohiro Sawa, Shigemoto Fujii, Takaaki Akaike
  • Organizer: The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide The 16th Annual Scientific Meeting of the Nitric Oxide Society of Japan
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-05-20
  • Int'l Joint Research
• [Presentation] シスタチオニンγリアーゼの一酸化窒素応答性とその意義 (2015)
  • Author(s): 中村麻里江、松本卓巳、松原守、高田剛、土屋幸弘、渡邊泰男
  • Organizer: 第１３２回日本薬理学会関東部会
  • Place of Presentation: 明海大学浦安キャンパス（浦安市）
  • Year and Date: 2015-07-04
• [Presentation] 活性イオウ分子産生酵素のNO応答性 (2015)
  • Author(s): 中村麻里江、松本卓巳、高田剛、土屋幸弘、井田智章、澤智裕、赤池孝章、渡邊泰男
  • Organizer: 第１５回日本NO学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター（豊中市）
  • Year and Date: 2015-06-26
• [Presentation] 活性システインパースルフィドのメタボロームおよびプロテオーム解析 (2015)
  • Author(s): 井田智章、居原秀、澤智裕、土屋幸弘、渡邊泰男、藤井重元、熊谷嘉人、本橋ほづみ、赤池孝章
  • Organizer: 第１５回日本NO学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター（豊中市）
  • Year and Date: 2015-06-26
• [Presentation] HPLC-蛍光検出法によるシステインパースルフィドの新しい定量システムの構築 (2015)
  • Author(s): ジョン ミンギョン、井田智章、笠松真吾、松永哲郎、土屋幸弘、渡邊泰男、藤井重元、赤池孝章
  • Organizer: 第１５回日本NO学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター（豊中市）
  • Year and Date: 2015-06-26