Au4 cluster inhibits human thioredoxin reductase activity via specifically binding of Au to Cys189
文献类型：期刊论文
| 作者 | Du, ZY; He, ZS; Fan, JD; Huo, YA; He, B; Wang, YR; Sun, QQ; Niu, WC; Zhao, WC; Zhao, LA |
| 刊名 | NANO TODAY
 |
| 出版日期 | 2022 |
| 卷号 | 47页码:101686 |
| ISSN号 | 1748-0132 |
| 关键词 | Human thioredoxin reductase Thioredoxin Au cluster Anti-tumor nanodrug |
| DOI | 10.1016/j.nantod.2022.101686 |
| 文献子类 | Article |
| 英文摘要 | Studies have shown that Au triggers tumor cell apoptosis by directly inhibiting human thioredoxin re-ductase (hTrxR), thus making Au potential drugs for cancer treatment. However, the exact molecular me-chanism of Au inhibiting hTrxR has never been demonstrated via experimental and theoretical studies. Here, we synthesized an Au4 cluster coated by an artificial RGD peptide. This gold cluster can bind with hTrxR (KD: & SIM;1.74 mu M) in vitro, and significantly inhibit hTrxR activity in tumor cells. To analyze the un-derlying mechanism, we established hTrxR-overexpressing tumor cells and fished Au-hTrxR adducts from tumor cells previously treated by Au clusters. Using single-particle cryo-electron microscopy (Cryo-EM) and mass spectra (MS), we found unexpectedly that, Au (I) ion, metabolism of Au cluster, specifically binds to the Cys189 of hTrxR. Molecular dynamic simulation revealed such specific Au-Cys189 binding effectively broke the electron transfer from Sec498 of hTrxR to Cys32 of thioredoxin. This inhibition of hTrxR activity by Au4 cluster induced ROS-regulated tumor cell apoptosis and significantly suppressed tumor growth in an A549 lung cancer xenograft model. In summary, this study revealed the structural mechanism of Au in-hibiting hTrxR activity and shed light to the design and application of novel hTrxR-inhibitory anti-tumor nanodrugs.(c) 2022 Elsevier Ltd. All rights reserved. |
| 电子版国际标准刊号 | 1878-044X |
| 语种 | 英语 |
| WOS记录号 | WOS:000896014900001 |
| 源URL | [http://ir.ihep.ac.cn/handle/311005/299926]  |
| 专题 | 高能物理研究所_多学科研究中心 高能物理研究所_粒子天体物理中心 |
| 作者单位 | 中国科学院高能物理研究所 |
| 推荐引用方式 GB/T 7714 | Du, ZY,He, ZS,Fan, JD,et al. Au4 cluster inhibits human thioredoxin reductase activity via specifically binding of Au to Cys189[J]. NANO TODAY,2022,47:101686. |
| APA | Du, ZY.,He, ZS.,Fan, JD.,Huo, YA.,He, B.,...&Gao, XY.(2022).Au4 cluster inhibits human thioredoxin reductase activity via specifically binding of Au to Cys189.NANO TODAY,47,101686. |
| MLA | Du, ZY,et al."Au4 cluster inhibits human thioredoxin reductase activity via specifically binding of Au to Cys189".NANO TODAY 47(2022):101686. |
入库方式： OAI收割
来源：高能物理研究所
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