中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 合肥物质科学研究院
  3. 中国科学院合肥物质科学研究院
Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis

文献类型：期刊论文

作者Zhou, Jiashen1; Zhang, Lin1; Zeng, Liping2,3,4; Yu, Lu5; Duan, Yuanyuan6; Shen, Siqi1; Hu, Jingyan1; Zhang, Pan7; Song, Wenyan1; Ruan, Xiaoxue8
刊名NATURE COMMUNICATIONS
出版日期2021-11-26
卷号12
DOI10.1038/s41467-021-27148-0
通讯作者Chen, Hong-Zhuan(hongzhuan_chen@hotmail.com) ; Cronan, John E.(jecronan@illinois.edu) ; Bi, Hongkai(hkbi@njmu.edu.cn) ; Zhang, Liang(liangzhang2014@sjtu.edu.cn)
英文摘要Unsaturated fatty acids (UFAs) are essential for functional membrane phospholipids in most bacteria. The bifunctional dehydrogenase/isomerase FabX is an essential UFA biosynthesis enzyme in the widespread human pathogen Helicobacter pylori, a bacterium etiologically related to 95% of gastric cancers. Here, we present the crystal structures of FabX alone and in complexes with an octanoyl-acyl carrier protein (ACP) substrate or with holo-ACP. FabX belongs to the nitronate monooxygenase (NMO) flavoprotein family but contains an atypical [4Fe-4S] cluster absent in all other family members characterized to date. FabX binds ACP via its positively charged alpha 7 helix that interacts with the negatively charged alpha 2 and alpha 3 helices of ACP. We demonstrate that the [4Fe-4S] cluster potentiates FMN oxidation during dehydrogenase catalysis, generating superoxide from an oxygen molecule that is locked in an oxyanion hole between the FMN and the active site residue His182. Both the [4Fe-4S] and FMN cofactors are essential for UFA synthesis, and the superoxide is subsequently excreted by H. pylori as a major resource of peroxide which may contribute to its pathogenic function in the corrosion of gastric mucosa. Helicobacter pylori FabX, a dehydrogenase/isomerase flavoprotein, is required for unsaturated fatty acid synthesis. Here, the authors characterize FabX substrate recognition and catalytic mechanism, and reveal that it contains an atypical [4Fe-4S] cluster, which is essential and participates in the catalytic cycle.
WOS关键词ESCHERICHIA-COLI ; MECHANISM ; REDUCTASE ; COMPLEX ; FLAVOPROTEIN ; MODEL ; CHAIN ; DEHYDRATASE ; SYNTHETASE ; SOFTWARE
资助项目Major Research plan of the National Natural Science Foundation of China[91853118] ; National Key R&D Programs of China[2018YFC0311003] ; National Key R&D Programs of China[2019YFA0405600] ; National Natural Science Foundation of China[22077081] ; National Natural Science Foundation of China[21722802] ; National Natural Science Foundation of China[82073899] ; National Natural Science Foundation of China[31570053] ; National Natural Science Foundation of China[31870029] ; National Natural Science Foundation of China[21927814] ; National Natural Science Foundation of China[U1732275] ; National Natural Science Foundation of China[21825703] ; Science and Technology Commission of Shanghai Municipality[20S11900300] ; Shuguang Program - Shanghai Education Development Foundation[20SG16] ; Shanghai Municipal Education Commission[20SG16] ; Innovative research team of high-level local universities in Shanghai[SSMU-ZLCX20180702] ; China Postdoctoral Science foundation[2020M681342] ; National Science Foundation of the Jiangsu Higher Education Institutions of China[18KJA310002] ; Jiangsu Specially Appointed Professor ; Jiangsu Medical Specialist Programs of China ; Jiangsu Province Innovative and Entrepreneurial Team Program ; National Institute of Allergy and Infectious Diseases, (NIH, USA) grant[AI15650]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者NATURE PORTFOLIO
WOS记录号WOS:000722939600010
资助机构Major Research plan of the National Natural Science Foundation of China ; National Key R&D Programs of China ; National Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality ; Shuguang Program - Shanghai Education Development Foundation ; Shanghai Municipal Education Commission ; Innovative research team of high-level local universities in Shanghai ; China Postdoctoral Science foundation ; National Science Foundation of the Jiangsu Higher Education Institutions of China ; Jiangsu Specially Appointed Professor ; Jiangsu Medical Specialist Programs of China ; Jiangsu Province Innovative and Entrepreneurial Team Program ; National Institute of Allergy and Infectious Diseases, (NIH, USA) grant
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/126788]  
专题中国科学院合肥物质科学研究院
通讯作者Chen, Hong-Zhuan; Cronan, John E.; Bi, Hongkai; Zhang, Liang
作者单位1.Shanghai Jiao Tong Univ, Dept Pharmacol & Chem Biol, State Key Lab Oncogenes & Related Genes, Sch Med, Shanghai 200025, Peoples R China
2.Nanjing Med Univ, Dept Pathogen Biol, Nanjing 211166, Jiangsu, Peoples R China
3.Nanjing Med Univ, Jiangsu Key Lab Pathogen Biol, Nanjing 211166, Jiangsu, Peoples R China
4.Nanjing Med Univ, Sir Run Run Hosp, Nanjing 211166, Jiangsu, Peoples R China
5.Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Peoples R China
6.Nanjing Med Univ, Lab Ctr Basic Med Sci, Nanjing 211166, Jiangsu, Peoples R China
7.Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Key Lab Med Epigenet & Metab, Shanghai 200032, Peoples R China
8.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China
9.Nanjing Univ Chinese Med, Sch Pharm, Jiangsu Key Lab Funct Subst Chinese Med, Nanjing 210023, Jiangsu, Peoples R China
10.Univ Sci & Technol China, Affiliated Hosp 1, Div Life Sci & Med, Hefei 230026, Anhui, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Jiashen,Zhang, Lin,Zeng, Liping,et al. Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis[J]. NATURE COMMUNICATIONS,2021,12.
APA Zhou, Jiashen.,Zhang, Lin.,Zeng, Liping.,Yu, Lu.,Duan, Yuanyuan.,...&Zhang, Liang.(2021).Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis.NATURE COMMUNICATIONS,12.
MLA Zhou, Jiashen,et al."Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis".NATURE COMMUNICATIONS 12(2021).

入库方式： OAI收割

来源：合肥物质科学研究院

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。