Development ofenzyme inlulkar far infectious diseace including malaria and clarification ofthe inlubitor activity
疟疾等远距离传染病酶的研制及其抑制剂活性的阐明
基本信息
- 批准号:18350086
- 负责人:
- 金额:$ 7.92万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2006
- 资助国家:日本
- 起止时间:2006 至 2007
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
人类疟疾、利什曼病、南美锥虫病、非洲锥虫病、登革热和血吸虫病等热带疾病继续造成大量发病和死亡。在这个项目中,我们进行了X-射线晶体学研究的重要酶寄生虫有关的三个这些传染病,构建结构基础的药物开发的二氧化硅方法。从大肠杆菌中分离纯化了乳清酸磷酸核糖基转移酶(pyr 5)和乳清酸核苷5 '-单磷酸脱羧酶(pyr 6),并对它们进行了结晶。结果,pyr 6的天然和产物UMP络合物形式结晶并进行X射线结构分析。pyr 6的脱辅基和复合形式的2.7和2.6 A解析结构提供了脱羧机制的细节(J. Biochem.,2008年)。对克氏锥虫和利什曼原虫的PGF合成酶也进行了结晶,并对克氏锥虫和利什曼原虫的PGF合成酶进行了结构分析。以1.7 A分辨率测定cruzi(Acta Cryst. F,2007)。并测定了PGF合成酶与吲哚美辛复合物的结构,为开发新的抑制剂提供了结构信息。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Structural basis for the decarboxylation of orotidine 5'-monophosphate (OMP) by Plasmodium Talon : Far= OMP decarboxylase.
疟原虫 Talon 使乳清苷 5-单磷酸 (OMP) 脱羧的结构基础:Far= OMP 脱羧酶。
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:K.;Tokuoka;et. al.
- 通讯作者:et. al.
Trypanosoma cruzi由来01d Yellow EnzymeのX線結晶構造解析
克氏锥虫 01d 黄色酶的 X 射线晶体结构分析
- DOI:
- 发表时间:2007
- 期刊:
- 影响因子:0
- 作者:N.;Okamoto;H. Okano;岡本尚毅
- 通讯作者:岡本尚毅
The Crystal Structure of Orotidine 5'-monophosphate Decarboxylase from the Human Malaria Parasite Plasmodium falciparm
人疟原虫恶性疟原虫乳清苷 5-单磷酸脱羧酶的晶体结构
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:K.;Tokuoka
- 通讯作者:Tokuoka
Crystal Structure analysis of Prostaglandin F_<2a> synthase.
前列腺素F_<2a>合酶的晶体结构分析。
- DOI:
- 发表时间:2007
- 期刊:
- 影响因子:0
- 作者:N.;Okamoto;H. Okano;岡本尚毅;徳岡啓司
- 通讯作者:徳岡啓司
Crystallization and preliminary X-ray analysis of the tRNA thiolation enzyme MnmA from Escherichia coli complexed with tRNA(Glu)
大肠杆菌 tRNA 硫醇化酶 MnMA 与 tRNA(Glu) 复合物的结晶和初步 X 射线分析
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Numata;T.;Ikeuchi;Y.;Fukai;S.;Adachi;H.;Matsumura;H.;Takano;K.;Murakami;S.;Inoue;T.;Mori;Y.;Sasaki;T.;Suzuki;T.;Nureki;O.
- 通讯作者:O.
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INOUE Tsuyoshi其他文献
Experimental study on stability of axial direction of Balance Piston mechanism
平衡活塞机构轴向稳定性实验研究
- DOI:
10.1299/transjsme.19-00187 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
HIRAKI Hiromichi;INOUE Tsuyoshi;YABUI Shota - 通讯作者:
YABUI Shota
Development of model for stability analysis in a balance piston mechanism in turbopump by using active control
利用主动控制开发涡轮泵平衡活塞机构稳定性分析模型
- DOI:
10.1299/transjsme.18-00445 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
YABUI Shota;HIRAKI Hiromichi;INOUE Tsuyoshi - 通讯作者:
INOUE Tsuyoshi
地図上のノード位置を制約とするMoving Horizon Estimationによる自動車位置の補正
使用地图上的节点位置作为约束,使用移动地平线估计来校正车辆位置
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
HIRAKI Hiromichi;INOUE Tsuyoshi;YABUI Shota;藤間 隆生,野中 謙一郎,関口 和真 - 通讯作者:
藤間 隆生,野中 謙一郎,関口 和真
INOUE Tsuyoshi的其他文献
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{{ truncateString('INOUE Tsuyoshi', 18)}}的其他基金
Development of a Rotor Model Considering the Crack Propagation due to Fatigue and the Method for Vibration Diagnosis and Prognostics of the Crack Growth
考虑疲劳裂纹扩展的转子模型的开发以及裂纹扩展的振动诊断和预测方法
- 批准号:
23560257 - 财政年份:2011
- 资助金额:
$ 7.92万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Toward understanding the initial conditions of star formation using realistic magnetohydrodynamics simulations
使用真实的磁流体动力学模拟来了解恒星形成的初始条件
- 批准号:
23740154 - 财政年份:2011
- 资助金额:
$ 7.92万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Neutron structure analysis of human PGD synthase for elucidation of the reaction mechanism activated by metal ions
人 PGD 合成酶的中子结构分析,阐明金属离子激活的反应机制
- 批准号:
22550152 - 财政年份:2010
- 资助金额:
$ 7.92万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of the identification method of both the depth and position of the breathing crack in the rotating shaft
转轴呼吸裂纹深度和位置识别方法的研制
- 批准号:
20560214 - 财政年份:2008
- 资助金额:
$ 7.92万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Exploration of connection rules regulating synchronous firing in the thalamus
调节丘脑同步放电连接规则的探索
- 批准号:
20770128 - 财政年份:2008
- 资助金额:
$ 7.92万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Studies on Molecular Biology of Prostaglandin Biosynthesis by parasitic Trypanosoma
寄生锥虫前列腺素生物合成的分子生物学研究
- 批准号:
14370087 - 财政年份:2002
- 资助金额:
$ 7.92万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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The effect of gelanicals on viral infectious desease in senium
凝胶类药物对老年人病毒感染性疾病的作用
- 批准号:
05454235 - 财政年份:1993
- 资助金额:
$ 7.92万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)