Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis
文献类型：期刊论文
| 作者 | Zhang, Lin1,2; Xiao, Jianfeng3; Xu, Jianrong1; Fu, Tianran1; Cao, Zhiwei1; Zhu, Liang1,2; Chen, Hong-Zhuan1,2; Shen, Xu3 ; Jiang, Hualiang3; Zhang, Liang1,2
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| 刊名 | CELL RESEARCH
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| 出版日期 | 2016-12 |
| 卷号 | 26期号:12页码:1330-1344 |
| ISSN号 | 1001-0602 |
| 关键词 | fatty acid biosynthesis dehydratase ACP complex structure |
| DOI | 10.1038/cr.2016.136 |
| 文献子类 | Article |
| 英文摘要 | Fatty acid biosynthesis (FAS) is a vital process in cells. Fatty acids are essential for cell assembly and cellular metabolism. Abnormal FAS directly correlates with cell growth delay and human diseases, such as metabolic syndromes and various cancers. The FAS system utilizes an acyl carrier protein (ACP) as a transporter to stabilize and shuttle the growing fatty acid chain throughout enzymatic modules for stepwise catalysis. Studying the interactions between enzymatic modules and ACP is, therefore, critical for understanding the biological function of the FAS system. However, the information remains unclear due to the high flexibility of ACP and its weak interaction with enzymatic modules. We present here a 2.55 angstrom crystal structure of type II FAS dehydratase FabZ in complex with holo-ACP, which exhibits a highly symmetrical FabZ hexamer-ACP3 stoichiometry with each ACP binding to a FabZ dimer subunit. Further structural analysis, together with biophysical and computational results, reveals a novel dynamic seesaw-like ACP binding and catalysis mechanism for the dehydratase module in the FAS system, which is regulated by a critical gatekeeper residue (Tyr100 in FabZ) that manipulates the movements of the beta-sheet layer. These findings improve the general understanding of the dehydration process in the FAS system and will potentially facilitate drug and therapeutic design for diseases associated with abnormalities in FAS. |
| WOS关键词 | ACYL CARRIER PROTEIN ; RAY SOLUTION SCATTERING ; SMALL-ANGLE SCATTERING ; HELICOBACTER-PYLORI ; BIOLOGICAL MACROMOLECULES ; METABOLIC SYNDROME ; PROSTATE-CANCER ; SYNTHASE ; INHIBITORS ; RESOLUTION |
| 资助项目 | National Natural Science Foundation of China[21572133] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[91413102] ; Program for Professors of Special Appointment (Eastern Scholar) at the Shanghai Institutions of Higher Learning[00000000] ; National Great Basic Science Project of China[2010CB529806] ; Ministry of Science and Technology of China[2015CB910304] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5873572 |
| 出版者 | INST BIOCHEMISTRY & CELL BIOLOGY |
| WOS记录号 | WOS:000394353000008 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275773]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Liang |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Dept Pharmacol & Chem Biol, Shanghai, Peoples R China; 2.Shanghai Univ Collaborat Innovat Ctr Translat Med, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Lin,Xiao, Jianfeng,Xu, Jianrong,et al. Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis[J]. CELL RESEARCH,2016,26(12):1330-1344. |
| APA | Zhang, Lin.,Xiao, Jianfeng.,Xu, Jianrong.,Fu, Tianran.,Cao, Zhiwei.,...&Zhang, Liang.(2016).Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis.CELL RESEARCH,26(12),1330-1344. |
| MLA | Zhang, Lin,et al."Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis".CELL RESEARCH 26.12(2016):1330-1344. |
入库方式： OAI收割
来源：上海药物研究所
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