Mechanism of leucine signaling of Thermus thermophilus

嗜热栖热菌亮氨酸信号传导机制

• 批准号: 22780084
• 负责人: TOMITA Takeo
• 金额: $ 2.58万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22780084/
• 关键词: 好熱菌; グルタミン酸脱水素酵素; アロステリック調節; グローバル調節; ロイシン; 遺伝子発現調節

We revealed that glutamate dehydrogenase(GDH) from Thermus thermophilus formed hetero-hexameric structure consisted from homologous two subunits ; catalytic subunit(GdhB) and regulatory subunit(GdhB), and this complex was subject to allosteric activation by hydrophobic amino acids especially leucine. We succeeded to determine the crystal structure of GdhA/GdhB/Leu complex and revealed the allosteric mechanism of GDH. GDH2 from human(hGDH2) is also subject to allosteric activation by leucine and we found that important residues for binding of leucine were conserved in hGDH2. The mutational analyses of hGDH2 revealed that hGDH2 was also allosterically activated by leucine with a similar manner with GDH from T. thermophilus.We also performed comprehensive analysis of gene regulation by means of DNA microarray tecnique and suggested that leucine was a signal of global regulation in T. thermophilus.

结果表明，嗜热栖热菌谷氨酸脱氢酶（GDH）形成由催化亚基（GdhB）和调节亚基（GdhB）组成的异源六聚体结构，该复合体可被疏水性氨基酸特别是亮氨酸变构激活。我们成功地确定了GdhA/GdhB/Leu复合物的晶体结构，揭示了GDH的变构机制。来自人的GDH 2（hGDH 2）也受到亮氨酸的变构活化，并且我们发现用于结合亮氨酸的重要残基在hGDH 2中是保守的。突变分析表明，hGDH 2也能被亮氨酸变构激活，其激活方式与T.我们还利用基因芯片技术对T. thermophilus的基因调控进行了综合分析，认为亮氨酸是T. thermophilus的一个全局调控信号。嗜热菌

项目成果

Mulecular mechanism for allosteric regulation of glutamatedehydrogenase from Thermus thermophilus

嗜热栖热菌谷氨酸脱氢酶变构调节的分子机制

• 发表时间: 2010
• 作者: 富田武郎;西山真
• 通讯作者: 西山真

化学

化学

• 发表时间: 2007
• 作者: 富崎欣也;三原久和;杉本直己・大道達雄;三好大輔・杉本直己;杉本直己・三好大輔
• 通讯作者: 杉本直己・三好大輔

Thermus thermophilus由来グルタミン酸脱水素酵素における活性調節の分子機構の解析

嗜热栖热菌谷氨酸脱氢酶活性调控的分子机制分析

• 发表时间: 2010
• 作者: 富田武郎;西山真
• 通讯作者: 西山真

高度好熱菌Thermus thermophilus由来グルタミン酸脱水素酵素のロイシンによるアロステリック調節の構造基盤

亮氨酸对嗜热栖热菌谷氨酸脱氢酶变构调节的结构基础

• 发表时间: 2011
• 作者: 富田武郎;葛山智久;西山真
• 通讯作者: 西山真

Mechanism of leucine-induced allosteric activation of glutamate dehydrogenase

亮氨酸诱导谷氨酸脱氢酶变构激活的机制

• 发表时间: 2011
• 作者: 富田武郎;西山真
• 通讯作者: 西山真