Identification and mechanistic analysis of an inhibitor of the CorC Mg2+ transporter
文献类型：期刊论文
| 作者 | Huang, Yichen1; Mu, Kaijie2; Teng, Xinyu1; Zhao, Yimeng1; Funato, Yosuke3; Miki, Hiroaki3; Zhu, Weiliang2 ; Xu, Zhijian2; Hattori, Motoyuki1
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| 刊名 | ISCIENCE
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| 出版日期 | 2021-04-23 |
| 卷号 | 24期号:4页码:38 |
| DOI | 10.1016/j.isci.2021.102370 |
| 通讯作者 | Xu, Zhijian(zjxu@simm.ac.cn) ; Hattori, Motoyuki(hattorim@fudan.edu.cn) |
| 英文摘要 | The CorC/CNNM family of Na+-dependent Mg2+ transporters is ubiquitously conserved from bacteria to humans. CorC, the bacterial CorC/CNNM family of proteins, is involved in resistance to antibiotic exposure and in the survival of pathogenic microorganisms in their host environment. The CorC/CNNM family proteins possess a cytoplasmic region containing the regulatory ATP-binding site. CorC and CNNM have attracted interest as therapeutic targets, whereas inhibitors targeting the ATP-binding site have not been identified. Here, we performed a virtual screening of CorC by targeting its ATP-binding site, identified a compound named IGN95a with inhibitory effects on ATP binding and Mg2+ export, and determined the cytoplasmic domain structure in complex with IGN95a. Furthermore, a chemical cross-linking experiment indicated that with ATP bound to the cytoplasmic domain, the conformational equilibrium of CorC was shifted more toward the inward-facing state of the transmembrane domain. In contrast, IGN95a did not induce such a shift. |
| WOS关键词 | CONE-ROD DYSTROPHY ; MOLECULAR-MECHANICS ; NUCLEOTIDE-BINDING ; CNNM ; MUTATIONS ; PROTEINS |
| 资助项目 | Ministry of Science and Technology of the People's Republic of China (National Key R&D Program of China)[2016YFA0502800] ; National Natural Science Foundation of China[32071234] ; key laboratory program of the Education Commission of Shanghai Municipality[ZDSYS14005] ; Japan Society for the Promotion of Science[JP26111007] ; Japan Society for the Promotion of Science[JP17H04041] ; Japan Society for the Promotion of Science[JP20H03515] ; Japan Society for the Promotion of Science[JP20K07312] ; Japan Society for the Promotion of Science[JP20H05508] ; Japan Society for the Promotion of Science[JP17K19396] ; Innovative Research Team of High-level Local Universities in Shanghai |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000642261700113 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297350]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Zhijian; Hattori, Motoyuki |
| 作者单位 | 1.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Shanghai Key Lab Bioact Small Mol, State Key Lab Genet Engn,Dept Physiol & Biophys,S, 2005 Songhu Rd, Shanghai 200438, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Osaka Univ, Res Inst Microbial Dis, Dept Cellular Regulat, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan |
| 推荐引用方式 GB/T 7714 | Huang, Yichen,Mu, Kaijie,Teng, Xinyu,et al. Identification and mechanistic analysis of an inhibitor of the CorC Mg2+ transporter[J]. ISCIENCE,2021,24(4):38. |
| APA | Huang, Yichen.,Mu, Kaijie.,Teng, Xinyu.,Zhao, Yimeng.,Funato, Yosuke.,...&Hattori, Motoyuki.(2021).Identification and mechanistic analysis of an inhibitor of the CorC Mg2+ transporter.ISCIENCE,24(4),38. |
| MLA | Huang, Yichen,et al."Identification and mechanistic analysis of an inhibitor of the CorC Mg2+ transporter".ISCIENCE 24.4(2021):38. |
入库方式： OAI收割
来源：上海药物研究所
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