Investigation of biosynthetic mechanism of cyclic tetrapyrrole: Construction and cyclization of hydroxymethylbilane
Project/Area Number |
15K07018
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Functional biochemistry
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Research Institution | Kurume University |
Principal Investigator |
SATO Hideaki 久留米大学, 医学部, 准教授 (60271996)
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Co-Investigator(Kenkyū-buntansha) |
東元 祐一郎 久留米大学, 医学部, 教授 (40352124)
杉島 正一 久留米大学, 医学部, 准教授 (30379292)
原田 二朗 久留米大学, 医学部, 講師 (10373094)
塚口 舞 (古澤舞) 久留米大学, 医学部, 助教 (40624094)
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Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | ヘム生合成 / ポルフィリン生合成 / テトラピロール / X線結晶構造解析 / 酵素反応機構 / X線結晶構造解析 / 酵素反応 / ポルフィリン / 阻害剤 |
Outline of Final Research Achievements |
We tried to clarify the reaction mechanism of the two enzymes involved in the construction and cyclization of tetrapyrrole, based on their crystal structure. In particular, hydroxymethylbilane synthase (HMBS) has a dipyrromethane cofactor and combines four molecules of porphobilinogen as substrates sequentially to form a linear tetrapyrrole, hydroxymethylbilane. We separated enzyme-substrates complexes depending on the number of bound substrates, and succeeded in X-ray crystal structure analysis of HMBS in complex with two substrate molecules. In its crystal structure, compared to the holo form with no substrate, the cofactor moved to the far side of the active site and the two substrate molecules located in the space where originally occupied by the cofactor. These results indicate that the active site of HMBS changes its conformation greatly during the tetrapyrrole construction from substrates.
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Report
(4 results)
Research Products
(145 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] Phytochemicals against advanced glycation end products (AGEs) and the receptor system2017
Author(s)
Yamagishi, S., Matsui, T., Ishibashi, Y., Abe, Y., Sakaguchi, T., Higashimoto, Y.
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Journal Title
Current Pharmaceutical Design
Volume: 23(8)
Issue: 8
Pages: 1135-1141
DOI
Related Report
Peer Reviewed
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[Journal Article] N-butanol extracts of noni suppress advanced glycation end products (AGEs)-induced inflammatory and thrombotic reactions in endothelial cells through its anti-oxidative properties2017
Author(s)
Ishibashi, Y., Matsui, T., Abe, Y., Sakaguchi, T., Higashimoto, Y., Yamagishi, S.
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Journal Title
BMC Complementary and Alternative Medicine
Volume: 17(1)
Issue: 1
Pages: 137-137
DOI
Related Report
Peer Reviewed / Open Access
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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
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Insights into the Proton Transfer Mechanism of a Bilin Reductase PcyA Following Neutron Crystallography.2015
Author(s)
Unno, M., Ishikawa-Suto, K., Kusaka, K., Tamada, T., Hagiwara, Y., Sugishima, M., Wada, K., Yamada, T., Tomoyori, K., Hosoya, T., Tanaka, I., Niimura, N, Kuroki, R., Inaka, K., Ishihara, M., Fukuyama, K.
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Journal Title
J. Am. Chem. Soc.
Volume: in press
Issue: 16
Pages: 5452-5460
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] DNA Aptamer Raised Against Advanced Glycation End Products (AGEs) Improves Glycemic Control and Decreases Adipocyte Size in Fructose-Fed Rats by Suppressing AGE-RAGE Axis2015
Author(s)
Ojima, A., Matsui, T., Nakamura, N., Higashimoto, Y., Ueda, S., Fukami, K., Okuda, S., Yamagishi, S.I.
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Journal Title
Hormone and Metabolic Research
Volume: 47(4)
Issue: 04
Pages: 253-258
DOI
Related Report
Peer Reviewed
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[Journal Article] Pigment epithelium-derived factor inhibits caveolin-induced interleukin‑8 gene expression and proliferation of human prostate cancer cells.2015
Author(s)
Matsui, T., Ojima, A., Higashimoto, Y., Taira, J., Fukami, K., Yamagishi, S.
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Journal Title
Oncol. Lett.
Volume: 10
Issue: 4
Pages: 2644-2648
DOI
Related Report
Peer Reviewed
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[Journal Article] Improvement of heme oxygenase-1-based heme sensor for quantifying free heme in biological samples2015
Author(s)
Junichi Taira, Yukinori Nakashima, Shun Yoshihara, Shinya Koga, Shinji Sueda, Hideyuki Komatsu, Yuichiro Higashimoto, Toru Takahashi, Nohito Tanioka, Hiroko Shimizu, Hiroshi Morimatsu, Hiroshi Sakamoto
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Journal Title
Analytical Biochemistry
Volume: 489
Pages: 50-52
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Development of a monoclonal antibody-based ELISA system for glyceraldehyde-derived advanced glycation end products.2015
Author(s)
Matsui, T., Joo, H.D., Lee, J.M., Ju, S.M., Tao, W.H., Higashimoto, Y., Fukami, K., Yamagishi, S.I.
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Journal Title
Immunol. lett.
Volume: 161
Issue: 2
Pages: 141-146
DOI
Related Report
Peer Reviewed
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[Journal Article] DNA aptamer raised against advanced glycation end products (AGEs) prevents abnormalities in electroretinogram of experimental diabetic retinopathy.2015
Author(s)
Maeda, S., Matsui, T., Ojima, A., Suematsu, M., Kaseda, K., Higashimoto, Y., Yamakawa, R., Yamagishi, S.
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Journal Title
Ophthalmic Res.
Volume: 54
Issue: 4
Pages: 175-180
DOI
Related Report
Peer Reviewed
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[Presentation] Crystal Structure of Biliverdin and NADP+ bound Biliverdin IXα Reductase2016
Author(s)
Sugishima Masakazu, Takao Haruna, Hirabayashi Kei, Kouriki Haruna, Nakaniwa Tetsuko, Hagiwara Yoshinori, Harada Jiro, Yamamoto Ken, Fukuyama Keiichi, Wada Kei
Organizer
9th International Conference on Heme Oxygenase Prague 2016
Place of Presentation
Prukyne Institute (Prague, Czech)
Year and Date
2016-09-14
Related Report
Int'l Joint Research
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[Presentation] Constructions and characterizations of mutants containing bacteriochlorophyll c, d, e, or f of the green sulfur bacterium Chlorobaculum limnaeum2015
Author(s)
J. Harada, Y. Shibata, M. Ryono, M. Teramura, K. Yamamoto, T. Mizoguchi, H. Tamiaki
Organizer
The International Chemical Congress of Pacific Basin Societies (Pacifichem 2015)
Place of Presentation
Honolulu, Hawaii (U.S.A.)
Year and Date
2015-12-15
Related Report
Int'l Joint Research
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