Octameric structure of the human bifunctional enzyme paics in purine biosynthesis
文献类型：期刊论文
| 作者 | Li, Shu-Xing; Tong, Yong-Ping; Xie, Xiao-Cong; Wang, Qi-Hai; Zhou, Hui-Na; Han, Yi; Zhang, Zhan-Yu; Gao, We; Li, Sheng-Guang; Zhang, Xuejun C. |
| 刊名 | Journal of molecular biology
 |
| 出版日期 | 2007-03-09 |
| 卷号 | 366期号:5页码:1603-1614 |
| 关键词 | Paics Saicars Airc Channeling Tunnel system |
| ISSN号 | 0022-2836 |
| DOI | 10.1016/j.jmb.2006.12.027 |
| 通讯作者 | Bi, ru-chang(rcbi@ibp.ac.cn) |
| 英文摘要 | Phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (paics) is an important bifunctional enzyme in de novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide carboxylase (airc) and 4-(n-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (saicars) activities. it becomes an attractive target for rational anticancer drug design, rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway. here, we report the crystal structure of human paics, the first in the entire paics family, at 2.8 angstrom resolution. it revealed that eight paics subunits, each composed of distinct airc and saicars domains, assemble a compact homo-octamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains. based on structural comparison and functional complementation analyses, the active sites of saicars and airc were identified, including a putative substrate c02-binding site. furthermore, four symmetry-related, separate tunnel systems in the paics octamer were found that connect the active sites of airc and saicars. this study illustrated the octameric nature of the bifunctional enzyme. each carboxylase active site is formed by structural elements from three airc domains, demonstrating that the octamer structure is essential for the carboxylation activity. furthermore, the existence of the tunnel system implies a mechanism of intermediate channeling and suggests that the quaternary structure arrangement is crucial for effectively executing the sequential reactions. in addition, this study provides essential structural information for designing paics-specific inhibitors for use in cancer chemotherapy. (c) 2006 elsevier ltd. all rights reserved. |
| WOS关键词 | AVIAN AICAR TRANSFORMYLASE ; ESCHERICHIA-COLI PURE ; CRYSTAL-STRUCTURE ; N-5-CARBOXYAMINOIMIDAZOLE RIBONUCLEOTIDE ; PROTEIN-STRUCTURE ; GALLUS-GALLUS ; MUTASE PURE ; CYCLOHYDROLASE ; INHIBITOR ; PATHWAY |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000244621100020 |
| 出版者 | ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2382610 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Bi, Ru-Chang |
| 作者单位 | 1.Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China 3.Beijing Forestry Univ, Coll Sci, Beijing 100083, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Shu-Xing,Tong, Yong-Ping,Xie, Xiao-Cong,et al. Octameric structure of the human bifunctional enzyme paics in purine biosynthesis[J]. Journal of molecular biology,2007,366(5):1603-1614. |
| APA | Li, Shu-Xing.,Tong, Yong-Ping.,Xie, Xiao-Cong.,Wang, Qi-Hai.,Zhou, Hui-Na.,...&Bi, Ru-Chang.(2007).Octameric structure of the human bifunctional enzyme paics in purine biosynthesis.Journal of molecular biology,366(5),1603-1614. |
| MLA | Li, Shu-Xing,et al."Octameric structure of the human bifunctional enzyme paics in purine biosynthesis".Journal of molecular biology 366.5(2007):1603-1614. |
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来源：中国科学院大学
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