Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis

Jiashen Zhou, Lin Zhang, Liping Zeng, Lu Yu, Yuanyuan Duan, Siqi Shen, Jingyan Hu, Pan Zhang, Wenyan Song, Xiaoxue Ruan, Jing Jiang, Yinan Zhang, Lu Zhou, Jia Jia, Xudong Hang, Changlin Tian, Houwen Lin, Hong-Zhuan Chen (), John E. Cronan (), Hongkai Bi () and Liang Zhang ()
Additional contact information
Jiashen Zhou: Shanghai Jiao Tong University School of Medicine
Lin Zhang: Shanghai Jiao Tong University School of Medicine
Liping Zeng: Nanjing Medical University
Lu Yu: Chinese Academy of Sciences
Yuanyuan Duan: Nanjing Medical University
Siqi Shen: Shanghai Jiao Tong University School of Medicine
Jingyan Hu: Shanghai Jiao Tong University School of Medicine
Pan Zhang: Fudan University
Wenyan Song: Shanghai Jiao Tong University School of Medicine
Xiaoxue Ruan: Fudan University
Jing Jiang: Nanjing University of Chinese Medicine
Yinan Zhang: Nanjing University of Chinese Medicine
Lu Zhou: Fudan University
Jia Jia: Nanjing Medical University
Xudong Hang: Nanjing Medical University
Changlin Tian: Chinese Academy of Sciences
Houwen Lin: Shanghai Jiao Tong University School of Medicine
Hong-Zhuan Chen: Shanghai University of Traditional Chinese Medicine
John E. Cronan: University of Illinois
Hongkai Bi: Nanjing Medical University
Liang Zhang: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27148-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27148-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27148-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().