Development ofenzyme inlulkar far infectious diseace including malaria and clarification ofthe inlubitor activity
Project/Area Number |
18350086
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Chemistry related to living body
|
Research Institution | Osaka University |
Principal Investigator |
INOUE Tsuyoshi Osaka University, Graduate School of Engineering, Division ofApplied Chemistry, Associate Professor (20263204)
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Co-Investigator(Kenkyū-buntansha) |
KAI Yasushi Fukui University, of Technology, Department of Environmental and Biotechnological Frontier Engineering, Professor (40029236)
MATSUMURA Hiroyoshi Osaka University, Graduate School of Engineering, Division ofApplied Chemistry, Assistant Professor (30324809)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥12,370,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2007: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
|
Keywords | Plasmodium falciparum / infectious desease / drug design / X-ray structure analysis |
Research Abstract |
Tropical diseases such as human malaria, leishmaniasis, Chagas disease, human African trypanosomiasis, dengue fever and schistosomiasis continue to cause significant morbidity and mortality. In this project, we performed X-ray crystallographic studies of important enzymes from parasite concerning three these infectious disease to construct the structural basis for the drug development by the in-silica method. The important enzymes are (1) two kinds of enzymes concerning the de novo synthesis of pyrimidine nucleotide from human malaria, (2) prostaglandin (PG) F synthases from parasites of Chagas' disease and Leishmania. Recombinant enzymes of orotate phosphoribosyltransferase (pyr5) and Orotidine 5'-monophosphate decarboxylase (pyr6) were purified from E.coli and crystallized. As the result, the native and product UMP complex form of pyr6 were crystallized and carried out with the X-ray structural analyses. The 2.7 and 2.6 A resolutional structures of apo- and complex forms of pyr6 provided the details of the decarboxylation mechanism (J. Biochem., 2008). As for the PGF synthases from Trypanosoma cruzi and Leishmania mejor were also performed crystallization and the structure of PGF synthase from T. cruzi were determined at 1.7 A resolution (Acta Cryst. F, 2007). The complex structure of PGF sytnthase with indomethacin were also determined, providing the structural information for new inhibitor development.
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Report
(3 results)
Research Products
(50 results)
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[Journal Article] Crystal structure of intein homing endonuclease II encoded in the DNA polymerase gene from Hyperthermophilic Archaeon Thermococcus kodakaraensis strain KOD12006
Author(s)
H.Matsumura, H.Takahashi, T.Inoue, T.Yamamoto, H.Hashimoto, M.Nishioka, S.Fujiwara, M.Takagi, T.Imanaka, Y.Kai
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Journal Title
Proteins : Structure Function, and Bioinformatics 63巻3号
Pages: 711-715
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[Journal Article] Application of Femtosecond Laser Ablation for Detaching Grown Protein Crystals from a Glass Capillary Tube2006
Author(s)
M.Kashii, R.Fujisawa, H.Adachi, Y.Mori, T.Sasaki, Y.Koga, K.Takano, S.Kanaya, H.Matsumura, T.Inoue, S.Murakami, K.Sugamoto, H.Yoshikawa
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Journal Title
Journal of Bioscience and Bioengineering 102巻4号
Pages: 372-374
NAID
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[Journal Article] Cooling-rate screening system for determining protein crystal growth conditions2006
Author(s)
R.Murai, S.Nakata, M.Kashii, H.Adachi, A.Niino, K.Takano, H.Matsumura, S.Murakami, T.Inoue, Y.Mori, T.Sasaki
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Journal Title
Journal of Crystal Growth 292巻2号
Pages: 433-436
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[Journal Article] Crystallization and preliminary crystallographic analysis of orotidine 5'-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum2006
Author(s)
S.R.Krungkrai, K.Tokuoka, Y.Kusakari, T.Inoue, H.Adachi, H.Matsumura, K.Takano, S.Murakami, Y.Mori, Y.Kai, J.Krungkrai, T.Horii
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Journal Title
Acta Crystallographica Section F 62巻6号
Pages: 542-545
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[Journal Article] Purification, crystallization and preliminary X-ray diffraction of SecDF, a translocon-associated membrane protein, from Thermus thermophilus2006
Author(s)
T.Tsukazaki, H.Mori, S.Fukai, T.Numata, A.Perederina, H.Adachi, H.Matsumura, K.Takano, S.Murakami, T.Inoue, Y.Mori, T.Sasaki, Dmitry, G.Vassylyev, O.Nureki, K.Ito
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Journal Title
Acta Crystallographica Section F 62巻4号
Pages: 376-380
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[Journal Article] Crystallization and preliminary X-ray analysis of the tRNA thiolation enzyme MnmA from Escherichia coli complexed with tRNA^<Glu>.2006
Author(s)
T.Numata, Y.Ikeuchi, S.Fukai, H.Adachi, H.Matsumura, K.Takano, S.Murakami, T.Inoue, Y.Mori, T.Sasaki, T.Suzuki, O.Nureki
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Journal Title
Acta Crystallographica Section F 62巻4号
Pages: 368-371
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[Book] 生物物理2007
Author(s)
井上豪, 裏出良博
Total Pages
8
Publisher
日本生物物理学会
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[Book] ファルマシア2007
Author(s)
井上豪, 福西快文, 坂田恒昭
Total Pages
5
Publisher
社団法人 日本薬学会
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[Book] 光学2007
Author(s)
安達宏昭, 森勇介, 佐々木孝友, 高野和文, 井上豪, 松村浩由, 村上聡
Total Pages
5
Publisher
日本光学会
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[Book] 酵素工学ニュース2006
Author(s)
安達宏昭, 森勇介, 佐々木孝友, 高野和文, 松村浩由, 井上豪, 村上聡
Total Pages
5
Publisher
酵素工学研究会
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