Crystal Structures of PI3K alpha Complexed with PI103 and Its Derivatives: New Directions forInhibitors Design
文献类型：期刊论文
| 作者 | Zhao Yanlong; Zhang Xi; Chen Yingyi; Lu Shaoyong; Peng Yuefeng; Wang Xiang; Guo Chengliang; Zhou Aiwu; Zhang Jingmiao; Luo Yu |
| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2014 |
| 英文摘要 | The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3Kα–PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3Kα–9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3Kα inhibitors. |
| 收录类别 | SCI |
| 原文出处 | http://pubs.acs.org/doi/abs/10.1021/ml400378e |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/6190]  |
| 专题 | 深圳先进技术研究院_其他 |
| 作者单位 | ACS MEDICINAL CHEMISTRY LETTERS |
| 推荐引用方式 GB/T 7714 | Zhao Yanlong,Zhang Xi,Chen Yingyi,et al. Crystal Structures of PI3K alpha Complexed with PI103 and Its Derivatives: New Directions forInhibitors Design[J]. ACS MEDICINAL CHEMISTRY LETTERS,2014. |
| APA | Zhao Yanlong.,Zhang Xi.,Chen Yingyi.,Lu Shaoyong.,Peng Yuefeng.,...&Zhang Jian.(2014).Crystal Structures of PI3K alpha Complexed with PI103 and Its Derivatives: New Directions forInhibitors Design.ACS MEDICINAL CHEMISTRY LETTERS. |
| MLA | Zhao Yanlong,et al."Crystal Structures of PI3K alpha Complexed with PI103 and Its Derivatives: New Directions forInhibitors Design".ACS MEDICINAL CHEMISTRY LETTERS (2014). |
入库方式： OAI收割
来源：深圳先进技术研究院
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