Structural Insight into Inactivation of Plasminogen Activator Inhibitor-1 by a Small-Molecule Antagonist
文献类型：期刊论文
| 作者 | Lin, Zhonghui1,2; Jensen, Jan K.2,3; Hong, Zebin1,2; Shi, Xiaoli1,2; Hu, Lihong4; Andreasen, Peter A.2,3; Huang, Mingdong1,2 |
| 刊名 | CHEMISTRY & BIOLOGY
 |
| 出版日期 | 2013-02-21 |
| 卷号 | 20期号:2页码:253-261 |
| ISSN号 | 1074-5521 |
| DOI | 10.1016/j.chembiol.2013.01.002 |
| 文献子类 | Article |
| 英文摘要 | Plasminogen activator inhibitor-1 (PAI-1), a serpin, is the physiological inhibitor of tissue-type and urokinase-type plasminogen activators and thus also an inhibitor of fibrinolysis and tissue remodeling. It is a potential therapeutic target in many pathological conditions, including thrombosis and cancer. Several types of PAI-1 antagonist have been developed, but the structural basis for their action has remained largely unknown. Here we report X-ray crystal structure analysis of PAI-1 in complex with a small-molecule antagonist, embelin. We propose a mechanism for embelin-induced rapid conversion of PAI-1 into a substrate for its target proteases and the subsequent slow conversion of PAI-1 into an irreversibly inactivated form. Our work provides structural clues to an understanding of PAI-1 inactivation by small-molecule antagonists and an important step toward the design of drugs targeting PAI-1. |
| WOS关键词 | BREAST-CANCER PATIENTS ; WEIGHT INHIBITOR ; PAI-1 INHIBITOR ; ARTERIAL THROMBOSIS ; SIGNALING PATHWAY ; MECHANISM ; TYPE-1 ; FIBRINOLYSIS ; BINDING ; SERPIN |
| 资助项目 | Natural Science Foundation of China[31161130356] ; Natural Science Foundation of China[30925040] ; Fujian province[2009I0029] ; Danish National Research Foundation[26-331-6] ; Lundbeck Foundation[R34.A3528] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000315978600017 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277728]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hu, Lihong |
| 作者单位 | 1.Chinese Acad Sci, Fujian Inst Res Struct Matter, State Key Lab Struct Chem, Fuzhou 350002, Peoples R China; 2.Aarhus Univ, Danish Chinese Ctr Proteases & Canc, DK-8000 Aarhus C, Denmark; 3.Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus C, Denmark; 4.Chinese Acad Sci, Shanghai Res Ctr Modernizat Tradit Chinese Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, Zhonghui,Jensen, Jan K.,Hong, Zebin,et al. Structural Insight into Inactivation of Plasminogen Activator Inhibitor-1 by a Small-Molecule Antagonist[J]. CHEMISTRY & BIOLOGY,2013,20(2):253-261. |
| APA | Lin, Zhonghui.,Jensen, Jan K..,Hong, Zebin.,Shi, Xiaoli.,Hu, Lihong.,...&Huang, Mingdong.(2013).Structural Insight into Inactivation of Plasminogen Activator Inhibitor-1 by a Small-Molecule Antagonist.CHEMISTRY & BIOLOGY,20(2),253-261. |
| MLA | Lin, Zhonghui,et al."Structural Insight into Inactivation of Plasminogen Activator Inhibitor-1 by a Small-Molecule Antagonist".CHEMISTRY & BIOLOGY 20.2(2013):253-261. |
入库方式： OAI收割
来源：上海药物研究所
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