Elucidation of the electron transfer mechanism from cytochrome P450 oxidoreductase to cytochrome P450
| Project/Area Number |
16K07280
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Kurume University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 秀明 久留米大学, 医学部, 准教授 (60271996)
坂本 寛 九州工業大学, 大学院情報工学研究院, 教授 (70309748)
福山 恵一 大阪大学, 工学研究科, 招へい研究員 (80032283)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | X線結晶構造解析 / タンパク質間相互作用 / 分子間相互作用 / 電子移動 / 酵素 / 電子伝達 / タンパク質複合体 / 相互作用 |
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| Outline of Final Research Achievements |
Cytochrome P450s are endoplasmic reticulum and mitochondria membrane-bound heme enzymes which activates molecular oxygen bound to the heme iron to catalyze the hydroxylation reaction of various lipids such as steroids and drugs.
Reducing equivalents must be supplied for P450 reaction and we tried to crystallize the complex of P450 and CPR which is one of the redox counterpart of P450. In the results of first screening, it is predicted that two kinds of P450s may form a stable complex with CPR, but it was not directly confirmed by the further analysis. Thus we conclude that these P450s are not suitable for the crystallization of the complex.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の結果はCPR-P450複合体の立体構造決定にはつながらなかったが、本複合体の構造決定が達成できれば、既知のCPR-HO複合体の立体構造との比較などにより、CPRという酵素の機能全般の理解へとつながると考えられる。また、CPR-P450複合体の立体構造からQM/MM法による量子化学計算を用いた電子移動反応の解析や、MDシミュレーションによるCPRのダイナミクスに関する研究の進展が期待される。
これらの研究はCPRに関する遺伝病であるAntley-Bixler症候群(指定難病の一つ)の治療法確立につながるかもしれない。
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Report
(4 results)
Research Products
(68 results)
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[Journal Article] A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity2017
Author(s)
Haruna Takao, Kei Hirabayashi, Yuki Nishigaya, Haruna Kouriki, Tetsuko Nakaniwa, Yoshinori Hagiwara, Jiro Harada, Hideaki Sato, Toshimasa Yamazaki, Yoichi Sakakibara, Masahito Suiko, Yujiro Asada, Yasuhiro Takahashi, Ken Yamamoto, Keiichi Fukuyama, Masakazu Sugishima, and Kei Wada
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Journal Title
Nat. Commun.
Volume: 8
Issue: 1
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A microfluidic-based protein crystallization method in 10 micrometer-sized crystallization space2016
Author(s)
Maeki M, Yamazaki S, Pawate SA, Ishida A, Tani H, Yamashita K, Sugishima M, Watanabe K, Tokeshi M, Kenis PJA, Miyazaki M
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Journal Title
CrystEngComm
Volume: 18
Issue: 40
Pages: 7722-7727
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Phosphonate-based irreversible inhibitors of human γ-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity2016
Author(s)
Akane Kamiyama, Mado Nakajima, Liyou Han, Kei Wada, Masaharu Mizutani, Yukio Tabuchi, Akiko Kojima-Yuasa, Isao Matsui-Yuasa, Hideyuki Suzuki, Keiichi Fukuyama, Bunta Watanabe, Jun Hiratake
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Journal Title
Bioorganic and Medical Chemistry
Volume: 24
Issue: 21
Pages: 5340-5352
DOI
Related Report
Peer Reviewed
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