Elucidation of Molecular Mechanism Responsible for Peroxidase Activity of a Heme-Nucleic Acid Complex through the Nature of an Axial H2O ligand and Its Application to Design of Novel Catalysts
Project/Area Number |
16KT0048
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Multi-year Fund |
Section | 特設分野 |
Research Field |
Transition State Control
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Research Institution | University of Tsukuba |
Principal Investigator |
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Project Period (FY) |
2016-07-19 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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Keywords | 四重鎖DNA / ヘム / G-カルテット / 酸化触媒作用 / テロメア / 機能性核酸 / 触媒機構 / 軸配位子 / 水分子 |
Outline of Final Research Achievements |
The molecular mechanism of the peroxidase activity of a complex composed of a G-quadruplex DNA formed from guanine-rich DNA and heme, found as prosthetic groups of various hemoproteins abundant in nature, has been elucidated. A water molecule (H2O) is located at the interface between the heme and DNA in the complex and is coordinated to the heme Fe atom. We found that the axial H2O in the complex is capable of being an electron-donating ligand which increases the Lewis basicity of the heme Fe atom to facilitate heterolytic O-O bond cleavage of Fe-bound peroxide (H2O2) to promote the formation of a high-valent iron(IV)oxo porphyrin π-cation radical.
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Academic Significance and Societal Importance of the Research Achievements |
ヘム核酸複合体の酸化触媒作用の遷移状態が軸配位子H2Oの電子的性質により調節される機構の解明を通して、H2Oの新しい機能が発見された。当該H2Oは、電子的性質が特異であるだけでなく、ヘム核酸複合体のヘムと四重鎖DNAの接触界面で孤立しているため、その運動性も特異である。これらの知見は、H2Oを利用する新しい反応の発見に役立つことが期待される。また、ヘムが核酸の補欠分子族として機能することから、ヘムタンパク質の機能を変えずにタンパク質部分を核酸で置換することが可能であることが示された。
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Report
(5 results)
Research Products
(85 results)
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[Journal Article] Characterization of Heme Orientational Disorder in a Myoglobin Reconstituted with a Trifluoromethyl-Group-Substituted Heme Cofactor2017
Author(s)
1.Yuki Kanai, Ayaka Harada, Tomokazu Shibata, Ryu Nishimura, Kosuke Namiki, Miho Watanabe, Shunpei Nakamura, Fumiaki Yuymoto, Toshiya Senda, Akihiro Suzuki, Saburo Neya, and Yasuhiko Yamamoto
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Journal Title
Biochemistry
Volume: 56
Issue: 34
Pages: 4500-4508
DOI
Related Report
Peer Reviewed
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[Journal Article] Effects of Heme Electronic Structure and Distal Polar Interaction on Functional and Vibrational Properties of Myoglobin2016
Author(s)
Y. Kanai, R. Nishimura, K. Nishiyama, T. Shibata, S. Yanagisawa, T. Ogura, T. Matsuo, S. Hirota, S. Neya, A. Suzuki, Y. Yamamoto
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Journal Title
Inorg. Chem.
Volume: 55
Issue: 4
Pages: 1613-1622
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Deoxyribozyme Possessing Heme2019
Author(s)
Y. Yamamoto, H. Araki, K. Hayasaka, S. Nakamura,T. Shibata, A. Momotake, and H. Hemmi
Organizer
61st Experimental Nuclear Magnetic Resonance Conference
Related Report
Int'l Joint Research
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[Presentation] Heme-DNAzyme2019
Author(s)
Y. Yamamoto, R. Shinomiya, H. Araki, T. Shibata, A. Momotake, S. Yanagisawa, T. Ogura, A. Suzuki, S. Neya, and H. Hemmi
Organizer
Commemorative International Symposium of the Japan Society of Nucleic Acids Chemistry
Related Report
Int'l Joint Research
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[Presentation] Heme Meets DNA.2019
Author(s)
Y. Yamamoto, R. Shinomiya, H. Kotani, H. Araki, A. Momotake, T. Shibata, S. Yanagisawa, T. Ogura, H. Hemmi, A. Suzuki, S. Neya, and T. Kojima
Organizer
19th International Conference on Biological Inorganic Chemistry (ICBIC-19)
Related Report
Int'l Joint Research / Invited
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[Presentation] DNAzyme Possessing Heme2019
Author(s)
Y. Yamamoto, R. Shinomiya, H. Araki, T. Shibata, A. Momotake, S. Yanagisawa, T. Ogura, A. Suzuki, and S. Neya
Organizer
The 46th International Symposium on Nucleic Acids Chemistry
Related Report
Int'l Joint Research
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[Presentation] Electronic Control of Myoglobin Function2019
Author(s)
T. Sugita, T. Matsuo, S. Hirota, S. Yanagisawa, T. Ogura, O. Shoji, Y. Watanabe, A. Suzuki, S. Neya, A. Momotake, and Y. Yamamoto
Organizer
17th International Symposium on Blood Substitutes & Oxygen Therapeutics (XVII-ISBS-2019)
Related Report
Int'l Joint Research
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[Presentation] Redox-catalyzing Deoxyribozymes Composed of Heme and DNAs2018
Author(s)
Y. Yamamoto, H. Araki, R. Shinomiya, K. Hayasaka, T. Shibata, A. Momotake, S. Yanagisawa, T. Ogura, H. Hemmi, A. Suzuki, and S. Neya
Organizer
9th Asian Biological Inorganic Chemistry Conference (AsBiC9)
Related Report
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[Presentation] Structure-function investigation of deoxyribozymes composed of heme and G-quadruplex DNAs2018
Author(s)
Y. Yamamoto, H. Araki, K. Hayasaka, R. Shinomiya, Y. Nakayama, K. Ochi, T. Shibata, A. Momotake, M. Hagihara, D. Sen, and H. Hemmi
Organizer
第57回NMR討論会(2018)
Related Report
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[Presentation] ヘムの系統的化学修飾および遠位アミノ酸置換がミオグロビンの機能に与える影響2017
Author(s)
渡邉美帆, 金井佑生, 西村龍, 柴田友和, 松尾貴史, 廣田俊, 柳澤幸子, 小倉尚志, 鈴木秋弘, 根矢三郎, 山本泰彦
Organizer
日本化学会 第97春季年会(2017)
Place of Presentation
慶応義塾大学日吉キャンパス(神奈川県横浜市)
Year and Date
2017-03-16
Related Report
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[Presentation] ヘムと四重鎖DNAの複合体の構造解析2017
Author(s)
越智健太郎, 山本泰彦, 柴田友和, 萩原正規, 逸見光
Organizer
日本化学会 第97春季年会(2017)
Place of Presentation
慶応義塾大学日吉キャンパス(神奈川県横浜市)
Year and Date
2017-03-16
Related Report
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[Presentation] Heme-DNA Complexes2017
Author(s)
Yasuhiko Yamamoto, Tomokazu Shibata, Yuya Katahira, Kentaro Ochi, Yusaku Nakayama, Hulin Tai, Akari Watanabe, Tomomi Nakao, Sachiko Yanagisawa, Takashi Ogura, Hikaru Hemmi, Masaki Hagihara, Akihiro Suzuki, and Saburo Neya
Organizer
14th International Symposium on Applied Bioinorganic Chemistry(ISABC14)
Related Report
Int'l Joint Research
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[Presentation] ヒトテロメア類似塩基配列の四重鎖DNAとヘム複合体のペルオキシダーゼ活性と構造の関係の解析2017
Author(s)
荒木はるか, 中山優作, 越智健太郎, 篠宮僚介, 柴田友和, 逸見光, 萩原正規, 小倉尚志, 柳澤幸子, 鈴木秋弘, 根矢三郎、Sen Dipankar, 山本泰彦
Organizer
日本化学会 第98春季年会 (2018)
Related Report
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[Presentation] Characterization of Complexes between Hemes and Parallel G-Quadruplex DNAs2016
Author(s)
Y. Yamamoto, T. Shibata, Y. Katahira, Y. Nakayama, H. Tai, T. Matsui, K. Morihashi, A. Watanabe, T. Nakao, S. Yanagisawa, T. Ogura, A. Suzuki, S. Neya
Organizer
8th Asian Bioligical Inorganic Chemistry Conference(AsBIC 8)
Place of Presentation
The University of Auckland (Auckland, New Zealand)
Year and Date
2016-12-04
Related Report
Int'l Joint Research
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