@article{efacb3d0846c4639a693ed931cbb0421,
title = "Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis",
abstract = "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 α7 helix that interacts with the negatively charged α2 and α3 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.",
author = "Jiashen Zhou and Lin Zhang and Liping Zeng and Lu Yu and Yuanyuan Duan and Siqi Shen and Jingyan Hu and Pan Zhang and Wenyan Song and Xiaoxue Ruan and Jing Jiang and Yinan Zhang and Lu Zhou and Jia Jia and Xudong Hang and Changlin Tian and Houwen Lin and Chen, {Hong Zhuan} and Cronan, {John E.} and Hongkai Bi and Liang Zhang",
note = "Funding Information: This project was supported by grants from the Major Research plan of the National Natural Science Foundation of China (No. 91853118 to Liang Zhang); the National Key R&D Programs of China (No. 2018YFC0311003 to H.B.; 2019YFA0405600 to L.Y.); the National Natural Science Foundation of China (Nos. 22077081, 21722802 to Liang Zhang; 82073899, 31570053, 31870029 to H.B.; 21927814, U1732275, 21825703 to C.T.); Science and Technology Commission of Shanghai Municipality (No. 20S11900300 to Liang Zhang); “Shuguang Program” supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (No. 20SG16 to Liang Zhang); Innovative research team of high-level local universities in Shanghai (No. SSMU-ZLCX20180702 to Liang Zhang); The fellowship of China Postdoctoral Science foundation (No. 2020M681342 to Lin Zhang); The National Science Foundation of the Jiangsu Higher Education Institutions of China (No. 18KJA310002 to H.B.); The Jiangsu Specially Appointed Professor and Jiangsu Medical Specialist Programs of China (to H.B.) and Jiangsu Province “Innovative and Entrepreneurial Team” Program (to H.B.) and National Institute of Allergy and Infectious Diseases, (NIH, USA) grant AI15650 (to J.E.C.). We thank the staffs from BL19U1 beamline of National Facility for Protein Science in Shanghai (NFPS) at Shanghai Synchrotron Radiation Facility (SSRF), for assistance during data collection. We thank Prof. James Imlay of the University of Illinois for his advice and Prof. Jiahai Zhou of the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences for providing anaerobic facilities. A portion of this work was performed on the Steady High Magnetic Field Facilities, High Magnetic Field Laboratory, Chinese Academy of Sciences. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-27148-0",
language = "English (US)",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}