Molecular mechanism of the allosteric regulation of the alpha gamma heterodimer of human NAD-dependent isocitrate dehydrogenase
2017-01-18
发表期刊SCIENTIFIC REPORTS (IF:3.8[JCR-2023],4.3[5-Year])
ISSN2045-2322
卷号7
发表状态已发表
DOI10.1038/srep40921
摘要Human NAD-dependent isocitrate dehydrogenase catalyzes the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate in the Krebs cycle. It exists as the alpha(2)beta gamma heterotetramer composed of the alpha beta and alpha gamma heterodimers. Previously, we have demonstrated biochemically that the alpha(2)beta gamma heterotetramer and alpha gamma heterodimer can be allosterically activated by citrate (CIT) and ADP. In this work, we report the crystal structures of the alpha gamma heterodimer with the gamma subunit bound without or with different activators. Structural analyses show that CIT, ADP and Mg2+ bind adjacent to each other at the allosteric site. The CIT binding induces conformational changes at the allosteric site, which are transmitted to the active site through the heterodimer interface, leading to stabilization of the ICT binding at the active site and thus activation of the enzyme. The ADP binding induces no further conformational changes but enhances the CIT binding through Mg2+-mediated interactions, yielding a synergistic activation effect. ICT can also bind to the CIT-binding subsite, which induces similar conformational changes but exhibits a weaker activation effect. The functional roles of the key residues are verified by mutagenesis, kinetic and structural studies. Our structural and functional data together reveal the molecular mechanism of the allosteric regulation of the alpha gamma heterodimer.
收录类别SCI
语种英语
资助项目Chinese Academy of Sciences[XDB08010302]
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000392191000001
出版者NATURE PUBLISHING GROUP
WOS关键词PIG-HEART ; OXIDATIVE DAMAGE ; KEY ROLE ; SACCHAROMYCES-CEREVISIAE ; CELLULAR DEFENSE ; KINETIC-ANALYSIS ; BINDING-SITES ; BETA-SUBUNIT ; IDH1 ; MUTATIONS
原始文献类型Article
引用统计
正在获取...
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1538
专题生命科学与技术学院_特聘教授组_丁建平组
通讯作者Ding, Jianping
作者单位
1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol,Ctr Excellence Mol Cell, Natl Ctr Prot Sci Shanghai,State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China
3.Chinese Acad Sci, Shanghai Sci Res Ctr, 333 Haike Rd, Shanghai 201210, Peoples R China
4.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, 2005 Songhu Rd, Shanghai 200438, Peoples R China
通讯作者单位生命科学与技术学院
推荐引用方式
GB/T 7714
Ma, Tengfei,Peng, Yingjie,Huang, Wei,et al. Molecular mechanism of the allosteric regulation of the alpha gamma heterodimer of human NAD-dependent isocitrate dehydrogenase[J]. SCIENTIFIC REPORTS,2017,7.
APA Ma, Tengfei,Peng, Yingjie,Huang, Wei,&Ding, Jianping.(2017).Molecular mechanism of the allosteric regulation of the alpha gamma heterodimer of human NAD-dependent isocitrate dehydrogenase.SCIENTIFIC REPORTS,7.
MLA Ma, Tengfei,et al."Molecular mechanism of the allosteric regulation of the alpha gamma heterodimer of human NAD-dependent isocitrate dehydrogenase".SCIENTIFIC REPORTS 7(2017).
条目包含的文件 下载所有文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
个性服务
查看访问统计
谷歌学术
谷歌学术中相似的文章
[Ma, Tengfei]的文章
[Peng, Yingjie]的文章
[Huang, Wei]的文章
百度学术
百度学术中相似的文章
[Ma, Tengfei]的文章
[Peng, Yingjie]的文章
[Huang, Wei]的文章
必应学术
必应学术中相似的文章
[Ma, Tengfei]的文章
[Peng, Yingjie]的文章
[Huang, Wei]的文章
相关权益政策
暂无数据
收藏/分享
文件名: 10.1038@srep40921.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。