Critical essence hidden in two catabolic enzymes for biological pigments

• Project/Area Number: 15K05555
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Tohoku University
• Principal Investigator: Matsui Toshitaka 東北大学, 多元物質科学研究所, 准教授 (90323120)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ヘム代謝 / 反応機構 / 結核菌 / 黄色ブドウ球菌 / 酸素添加 / 酵素反応 / 病原性細菌 / 酸素活性化 / 蛍光タンパク質 / 水酸化ヘム / １原子酸素添加 / ２原子酸素添加

Outline of Final Research Achievements

In this study, we have elucidated unique reaction mechanisms of new-type heme-degrading enzymes, MhuD from Mycobacterium tuberculosis and IsdG from Staphylococcus aureus, both of which bind heme in highly distorted conformation. MhuD successively catalyzes mono- and di-oxygenation reactions in a single active site. This is the first discovery of the enzyme that fuses the two distinct reactions, leading to the produce the unique heme catabolites of MhuD. Reaction analysis on IsdG reveals, contrary to previous reports, that the MhuD-type reaction becomes dominant under normal reaction conditions. The HCHO release reported is enhanced by increasing reduction rates. This mechanism may be biologically relevant to regulate the HCHO biosynthesis in S. aureus. Furthermore, fluorogenic proteins that bind new heme catabolites as pigments have been developed mainly for their detection with high sensitivity.

Research Products

• [Int'l Joint Research] Albert Einstein College of Medicine(米国)
• [Int'l Joint Research] Universite Grenoble/Universite Pierre et Marie Curie(France)
• [Int'l Joint Research] UC Irvine(米国)
• [Journal Article] Reaction Intermediates in the heme degradation reaction by HutZ from Vibrio cholerae (2017)
  • Author(s): Uchida*, T., Sekine, Y., Dojun, N., Lewis, A., Ishigami, I., Matsui, T., Yeh, S.-R., and Ishimori, K.
  • Journal Title: Dalton Transactions Volume: 46 Issue: 25 Pages: 8104-8109
  • DOI: 10.1039/c7dt01562c
  • NAID: 120006486794
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Artificial Hydrogenases based on Cobaloximes and Heme Oxygenase (2016)
  • Author(s): M. Bacchi, E. Veinberg, M. J. Field, J. Niklas, T. Matsui, D. M Tiede, O. G. Poluektov, M. Ikeda-Saito, M. Fontecave V. Artero
  • Journal Title: ChemPlusChem Volume: 81 Issue: 10 Pages: 1083-1089
  • DOI: 10.1002/cplu.201600218
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Charge-state-distribution analysis of Bach2 intrinsically disordered heme binding (2016)
  • Author(s): T. Suenaga, M. Watanabe-Matsui, H. Shima, T. Matsui, M. Ikeda-Saito, K. Igarashi, K. Murayama
  • Journal Title: J. Biochem. Volume: 160 Issue: 5 Pages: 291-298
  • DOI: 10.1093/jb/mvw035
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Unique coupling of mono- and dioxygenase chemistries in a single active site promotes heme degradation (2016)
  • Author(s): Toshitaka Matsui, Shusuke Nambu, Celia W. Goulding, Satoshi Takahashi, Hiroshi Fujii, Masao Ikeda-Saito
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 113 Issue: 14 Pages: 3779-3784
  • DOI: 10.1073/pnas.1523333113
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 黄色ブドウ球菌 IsdG におけるヘム代謝生成物の制御機構 (2017)
  • Author(s): 篠崎玲香, 松井敏高
  • Organizer: 第44回 生体分子科学討論会
• [Presentation] Unusual Degradation of Highly Distorted Heme: Its Mechanism and Precise Control (2017)
  • Author(s): Toshitaka Matsui
  • Organizer: The 2nd International Symposium on Stimuli-responsive Chemical Species for the Creation of Functional Molecules
  • Int'l Joint Research
• [Presentation] Functional coupling of mono- and dioxygenase chemistries in a single active site promotes unique heme degradation (2016)
  • Author(s): Toshitaka Matsui
  • Organizer: Japan-Korea-Taiwan Bioinorganic Chemistry Symposium
  • Place of Presentation: Okazaki Conference Center (Okazaki, Japan)
  • Year and Date: 2016-09-30
  • Int'l Joint Research / Invited
• [Presentation] ２種の酸素添加反応の融合による特異なヘム分解 (2016)
  • Author(s): 松井 敏高, 齋藤正男
  • Organizer: 第８９回 日本生化学大会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-09-27
• [Presentation] Unusual heme degradation achieved by unprecedented coupling of two distinct oxygenation modes (2016)
  • Author(s): Toshitaka Matsui, Shusuke Nambu, Masao Ikeda-Saito
  • Organizer: ICPP-9 (Ninth International Conference on Porphyrins and Phthalocyanines)
  • Place of Presentation: Nanjing, China
  • Year and Date: 2016-07-08
  • Int'l Joint Research / Invited
• [Presentation] ２種の酸素添加反応の融合による特殊なヘム分解 (2016)
  • Author(s): 松井敏高, 高橋聡, 齋藤正男, 藤井浩
  • Organizer: 第26回 金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 北大学術交流会館（北海道・札幌市）
  • Year and Date: 2016-06-18
• [Presentation] Unusual oxygenation mechanism of MhuD, a heme degrading enzyme from Mycobacterium tuberculosis (2015)
  • Author(s): Toshitaka Matsui, Shusuke Nambu, Masao Ikeda-Saito
  • Organizer: Pacifichem 2015
  • Place of Presentation: Sheraton Waikiki (Honolulu, USA)
  • Year and Date: 2015-12-19
  • Int'l Joint Research / Invited
• [Presentation] Unique reaction products of IsdG-type heme-degrading enzymes (2015)
  • Author(s): Toshitaka Matsui, Shusuke Nambu, Yukari Ono, Kohei Tsumoto, Masao Ikeda-Saito
  • Organizer: Pacifichem 2015
  • Place of Presentation: Hawaii Convention Center (Honolulu, USA)
  • Year and Date: 2015-12-16
  • Int'l Joint Research
• [Presentation] 異種機能の融合による特殊なヘム分解機構 (2015)
  • Author(s): 松井敏高, 齋藤正男
  • Organizer: 第9回バイオ関連化学シンポジウム
  • Place of Presentation: 熊本大学工学部（熊本県熊本市）
  • Year and Date: 2015-09-10
• [Presentation] ヘムの色んな壊し方 (2015)
  • Author(s): 松井敏高
  • Organizer: 北大・構造化学セミナー “New Frontier of Biostructural Chemistry in Hokkaido University”
  • Place of Presentation: 北海道大学理学部（北海道札幌市）
  • Year and Date: 2015-08-22
  • Invited
• [Presentation] Unusual oxygenation mechanism of MhuD, a heme degrading enzyme from Mycobacterium tuberculosis (2015)
  • Author(s): Toshitaka Matsui, Shusuke Nambu, Masao Ikeda-Saito
  • Organizer: "Metals in Biology" in Wako
  • Place of Presentation: 理研・鈴木梅太郎記念ホール（埼玉県和光市）
  • Year and Date: 2015-06-16
  • Int'l Joint Research
• [Presentation] 結核菌MhuDによる特殊な酸素添加反応 (2015)
  • Author(s): 松井 敏高, 南部 周介, 齋藤 正男
  • Organizer: 第42回生体分子科学討論会
  • Place of Presentation: 高崎シティギャラリー（群馬県高崎市）
  • Year and Date: 2015-06-12
• [Remarks] 東北大学プレスリリース
  • URL: http://www.tohoku.ac.jp/japanese/2016/03/press20160330-01.html