| Crystal Structures of Urokinase-type Plasminogen Activator in Complex with 4-（Aminomethyl） Benzoic Acid and 4-（Aminomethyl-phenyl）-methanol |
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| 引用本文： | 江龙光,赵更香,卞传兵,袁彩,黄子祥,黄明东.Crystal Structures of Urokinase-type Plasminogen Activator in Complex with 4-（Aminomethyl） Benzoic Acid and 4-（Aminomethyl-phenyl）-methanol[J].结构化学,2009,28(2):253-259. |
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| 作者姓名： | 江龙光 赵更香 卞传兵 袁彩 黄子祥 黄明东 |
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| 作者单位： | JIANG Long-Guang,ZHAO Geng-Xiang(State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,The Chinese Academy of Sciences,Fuzhou,Fujian 350002,China;Graduate School of the Chinese Academy of Sciences,Beijing 100039,China);BIAN Chuan-Bing,YUAN Cai,HUANG Zi-Xiang,HUANG Ming-Dong(State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,The Chinese Academy of Sciences,Fuzhou,Fujian 350002,China)
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| 基金项目： | 国家自然科学基金，国家重点基础研究发展规划(973计划)，Young Talent Programme of Fujian Province |
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| 摘 要： | Urokinase-type plasminogen activator （uPA） is a trypsin-like serine protease and plays a key role in several biological processes, including tissue remodeling, cell migration, and matrix degradation. The inhibitors of uPA have been shown to prevent the spread of metastasis and tumor growth, and accordingly uPA is widely recognized as a target for the treatment of cancer. In this work, we report the crystal structures of the complexes of uPA with its inhibitors： 4- （aminomethyl）-benzoic acid （AMBA） and 4-（aminomethyl-phenyl）-methanol （AMPM）, both at a resolution of 2.35 А. The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that AMBA is a better inhibitor for uPA （Ki = 2.68 mM） than AMPM （Ki = 13.99 mM）. The structural study shows that the binding mode of inhibitor AMBA on uPA is similar to that of AMPM on uPA, both docked into the active site S1 pocket of uPA. Structural details of these complexes are provided to explain the difference of inhibitory constants.
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| 关 键 词： | 尿激酶-血浆酶原催化剂 4-(氨甲基)安息香酸 (4-氨甲基-苯基)-甲醇 酶抑制实验 |
Crystal Structures of Urokinase-type Plasminogen Activator in Complex with 4-(Aminomethyl) Benzoic Acid and 4-(Aminomethyl-phenyl)-methanol |
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| JIANG Long-Guang,ZHAO Geng-Xiang,BIAN Chuan-Bing,YUAN Cai,HUANG Zi-Xiang,HUANG Ming-Dong.Crystal Structures of Urokinase-type Plasminogen Activator in Complex with 4-(Aminomethyl) Benzoic Acid and 4-(Aminomethyl-phenyl)-methanol[J].Chinese Journal of Structural Chemistry,2009,28(2):253-259. |
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| Authors: | JIANG Long-Guang ZHAO Geng-Xiang BIAN Chuan-Bing YUAN Cai HUANG Zi-Xiang HUANG Ming-Dong |
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| Institution: | 1. State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,The Chinese Academy of Sciences,Fuzhou,Fujian 350002,China;Graduate School of the Chinese Academy of Sciences,Beijing 100039,China
2. State Key Laboratory of Structural Chemistry,Fujian Institute of Research on the Structure of Matter,The Chinese Academy of Sciences,Fuzhou,Fujian 350002,China |
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| Abstract: | Urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease and plays a key role in several biological processes, including tissue remodeling, cell migration, and matrix degradation. The inhibitors of uPA have been shown to prevent the spread of metastasis and tumor growth, and accordingly uPA is widely recognized as a target for the treatment of cancer. In this work, we report the crystal structures of the complexes of uPA with its inhibitors: 4-(aminomethyl)-benzoic acid (AMBA) and 4-(aminomethyl-phenyl)-methanol (AMPM), both at a resolution of 2.35 A. The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that AMBA is a better inhibitor for uPA (Ki = 2.68 mM) than AMPM (Ki = 13.99 mM). The structural study shows that the binding mode of inhibitor AMBA on uPA is similar to that of AMPM on uPA, both docked into the active site S1 pocket of uPA. Structural details of these complexes are provided to explain the difference of inhibitory constants. |
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| Keywords: | uroktnase-type plasminogen activator 4-(aminomethyl)benzoic acid (4-aminomethyl-phenyl)-methanol enzyme inhibition assays contact area |
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