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| The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase | |
| 2017-01-31 | |
| Source Publication | SCIENTIFIC REPORTS
 |
| ISSN | 2045-2322 |
| Volume | 7 |
| Status | 已发表 |
| DOI | 10.1038/srep41882 |
| Abstract | Human NAD-dependent isocitrate dehydrogenase existing as the alpha(2)beta gamma heterotetramer, catalyzes the decarboxylation of isocitrate into a-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory beta and gamma subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing alpha beta and alpha gamma heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that alpha beta and alpha gamma alone have considerable basal activity but the full activity of alpha(2)beta gamma requires the assembly and cooperative function of both heterodimers. alpha(2)beta gamma and alpha gamma can be activated by citrate or/and ADP, whereas alpha beta cannot. The binding of citrate or/and ADP decreases the S-0.5,S- isocitrate and thus enhances the catalytic efficiencies of the enzymes, and the two activators can act independently or synergistically. Moreover, ATP can activate alpha(2)beta gamma and alpha gamma at low concentration and inhibit the enzymes at high concentration, but has only inhibitory effect on alpha beta. Furthermore, the allosteric activation of alpha(2)beta gamma is through the. subunit not the gamma subunit. These results demonstrate that the. subunit plays regulatory role to activate the holoenzyme, and the gamma subunit the structural role to facilitate the assembly of the holoenzyme. |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | Chinese Academy of Sciences[XDB08010302] |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000393082000001 |
| Publisher | NATURE PUBLISHING GROUP |
| WOS Keyword | AMINO-ACID-SEQUENCES ; PIG-HEART ; BOVINE HEART ; MOLECULAR-CLONING ; MANGANOUS ION ; BINDING-SITES ; ADP ; IDENTIFICATION ; PURIFICATION ; MUTATIONS |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1526 |
| Collection | 生命科学与技术学院_特聘教授组_丁建平组 |
| Corresponding Author | Ding, Jianping |
| Affiliation | 1.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, State Key Lab Mol Biol,Shanghai Inst Biol Sci, Ctr Excellence Mol Cell Sci,Inst Biochem & Cell B, 320 Yueyang Rd, Shanghai 200031, Peoples R China 2.Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 4.Chinese Acad Sci, Shanghai Sci Res Ctr, 333 Haike Rd, Shanghai 201210, Peoples R China 5.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, 2005 Songhu Rd, Shanghai 200438, Peoples R China |
| Corresponding Author Affilication | School of Life Science and Technology |
| Recommended Citation GB/T 7714 | Ma, Tengfei,Peng, Yingjie,Huang, Wei,et al. The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase[J]. SCIENTIFIC REPORTS,2017,7. |
| APA | Ma, Tengfei,Peng, Yingjie,Huang, Wei,Liu, Yabing,&Ding, Jianping.(2017).The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase.SCIENTIFIC REPORTS,7. |
| MLA | Ma, Tengfei,et al."The beta and gamma subunits play distinct functional roles in the alpha(2)beta gamma heterotetramer of human NAD-dependent isocitrate dehydrogenase".SCIENTIFIC REPORTS 7(2017). |
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