Structures of Trypanosome Vacuolar Soluble Pyrophosphatases: Antiparasitic Drug Targets
文献类型：期刊论文
| 作者 | Yang, Yunyun1,2; Ko, Tzu-Ping3; Chen, Chun-Chi2; Huang, Guozhong4,5; Zheng, Yingyin2; Liu, Weidong2; Wang, Iren3; Ho, Meng-Ru3; Hsu, Shang-Te Danny3; O'Dowd, Bing6 |
| 刊名 | ACS CHEMICAL BIOLOGY
 |
| 出版日期 | 2016-05-01 |
| 卷号 | 11期号:5页码:1362-1371 |
| 英文摘要 | Trypanosomatid parasites are the causative agents of many neglected tropical diseases, including the leishmaniases, Chagas disease, and human African trypanosomiasis. They exploit unusual vacuolar soluble pyrophosphatases (VSPs), absent in humans, for cell growth and virulence and, as such, are drug targets. Here, we report the crystal structures of VSP1s from Trypanosoma cruzi and T. brucei, together with that of the T. cruzi protein bound to a bisphosphonate inhibitor. Both VSP1s form a hybrid structure containing an (N-terminal) EF-hand domain fused to a (C-terminal) pyrophosphatase domain. The two domains are connected via an extended loop of about 17 residues. Crystallographic analysis and size exclusion chromatography indicate that the VSP1s form tetramers containing head-to-tail dimers. Phosphate and diphosphate ligands bind in the PPase substrate-binding pocket and interact with several conserved residues, and a bisphosphonate inhibitor (BPH-1260) binds to the same site. On the basis of Cytoscape and other bioinformatics analyses, it is apparent that similar folds will be found in most if not all trypanosomatid VSP1s, including those found in insects (Angomonas deanei, Strigomonas culicis), plant pathogens (Phytomonas spp.), and Leishmania spp. Overall, the results are of general interest since they open the way to structure-based drug design for many of the neglected tropical diseases. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | METAL-ION-BINDING ; INORGANIC PYROPHOSPHATASE ; POLYPHOSPHATE METABOLISM ; EF-HAND ; MECHANISM ; BRUCEI ; CRUZI ; ACIDOCALCISOMES ; LEISHMANIA ; PHOSPHATE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000376473600025 |
| 源URL | [http://124.16.173.210/handle/834782/2251]  |
| 专题 | 天津工业生物技术研究所_结构生物学与蛋白酶学实验室 郭瑞庭_期刊论文 |
| 作者单位 | 1.Tianjin Univ Sci & Technol, Coll Biotechnol, Tianjin 300457, Peoples R China 2.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Ind Enzymes Natl Engn Lab, Tianjin 300308, Peoples R China 3.Acad Sinica, Inst Biol Chem, Taipei 115, Taiwan 4.Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA 5.Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA 6.Univ Illinois, Dept Chem, Urbana, IL 61801 USA |
| 推荐引用方式 GB/T 7714 | Yang, Yunyun,Ko, Tzu-Ping,Chen, Chun-Chi,et al. Structures of Trypanosome Vacuolar Soluble Pyrophosphatases: Antiparasitic Drug Targets[J]. ACS CHEMICAL BIOLOGY,2016,11(5):1362-1371. |
| APA | Yang, Yunyun.,Ko, Tzu-Ping.,Chen, Chun-Chi.,Huang, Guozhong.,Zheng, Yingyin.,...&Guo, Rey-Ting.(2016).Structures of Trypanosome Vacuolar Soluble Pyrophosphatases: Antiparasitic Drug Targets.ACS CHEMICAL BIOLOGY,11(5),1362-1371. |
| MLA | Yang, Yunyun,et al."Structures of Trypanosome Vacuolar Soluble Pyrophosphatases: Antiparasitic Drug Targets".ACS CHEMICAL BIOLOGY 11.5(2016):1362-1371. |
入库方式： OAI收割
来源：天津工业生物技术研究所
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