Synthesis of functional probes toward elucidation of the function of respiratory enzymes of Caenorhabditis elegans.

合成功能探针以阐明秀丽隐杆线虫呼吸酶的功能。

• 批准号: 15380083
• 负责人: MIYOSHI Hideto
• 金额: $ 8.77万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15380083/
• 关键词: Respiratory Inhibitor; Respiratory Enzymes; Mitochondria; アセトゲニン; 構造活性相関

To identify the binding subunit of fenpyroximate, a very potent inhibitor of bovine heart mitochondrial complex I, we synthesized ^3H-labeled photolabile fenpyroximate ([^3H](trifluoromethyl)-phenyldiazirinyl fenpyroximate, TDF). TDF appeared to elicit very potent inhibition of bovine heart mitochondrial complex I being nearly equivalent to that of fenpyroximate.On the basis of photoaffinity studies with bovine heart complex I in collaboration with Dr.Takao Yagi (The Scripps Research Institute, USA), the binding site of TDF was shown to be subunit ND5 which is thought to exist in membrane arm of the enzyme. Since antibody to the C-terminal region of the ND5 subunit only weakly recognized the subunit, we identified the ND5 by 2D-electrophoresis (SDS-PAGE). Our result is the first study wherein the subunit located in membrane arm was identified as the inhibitor binding subunit. Our study strongly suggests that subunit(s) located in membrane arm may be involved in the proton-pumping activity of complex I.

为了鉴定唑螨酯（一种非常有效的牛心脏线粒体复合物I抑制剂）的结合亚基，我们合成了^3H标记的光不稳定的唑螨酯（[^3H]（三氟甲基）-苯基重氮丙啶基唑螨酯，TDF）。基于与TakaoYagi博士（TheScrippsResearchInstitute，USA）合作的牛心脏复合物I的光亲和性研究，TDF的结合位点显示为亚基ND 5，其被认为存在于酶的膜臂中.由于ND 5亚基C-末端区域的抗体仅弱识别该亚基，我们通过2D-电泳（SDS-PAGE）鉴定了ND 5。我们的结果是第一个研究，其中位于膜臂的亚基被确定为抑制剂结合亚基。我们的研究有力地表明，位于膜臂的亚基可能参与了复合物I的质子泵活性。

项目成果

Synthesis and mitochondrial complex I inhibition of dihydroxy-cohibin A, non-THF annonaceous acetogenin analogue

• DOI: 10.1016/j.bmcl.2003.11.057
• 发表时间: 2004-02-09
• 期刊: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
• 影响因子: 2.7
• 作者: Konno, H;Hiura, N;Miyoshi, H
• 通讯作者: Miyoshi, H

安部真人: "Essential structural features of acetogenins : role of hydroxy groups adjacent to the bis-THF ring"Bioorg.Med.Chem.Lett.. 14. 779-782 (2004)

Masato Abe：“Acetogenins 的基本结构特征：与双 THF 环相邻的羟基的作用”Bioorg.Med.Chem.Lett.. 14. 779-782 (2004)

Isolation and characterization of the stage-specific cytochrome b small subunit (CybS) of Ascaris suum complex II from the aerobic respiratory chain of larval mitochondria

• DOI: 10.1016/s0166-6851(03)00074-4
• 发表时间: 2003-05-01
• 期刊: MOLECULAR AND BIOCHEMICAL PARASITOLOGY
• 影响因子: 1.5
• 作者: Amino, H;Osanai, A;Kita, K
• 通讯作者: Kita, K

Synthesis and inhibition mechanism of Dlac-acetogenins : a novel type of inhibitor of bovine heart mitochondrial complex I.

Dlac-acetogenins 的合成和抑制机制：一种新型牛心线粒体复合物 I 抑制剂。

• 发表时间: 2005
• 期刊: Biochemistry 44
• 作者: 小田晃;長谷川祐治;水山高久;宮本邦明;野中理伸;宮本邦明;一丸直哉他
• 通讯作者: 一丸直哉他

Asymmetric binding of the high-affinity QH•- ubisemiquinone in quinol oxidase (bo3) from Escherichia coli studied by multifrequency electron paramagnetic resonance spectroscopy

• DOI: 10.1021/bi034010z
• 发表时间: 2003-05-20
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Grimaldi, S;Ostermann, T;MacMillan, F
• 通讯作者: MacMillan, F