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

Author

Listed:
  • 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
    University of Science and Technology of China)

  • 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)

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.

Suggested Citation

  • 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, 2021. "Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27148-0
    DOI: 10.1038/s41467-021-27148-0
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    1. Yolanda Y. Huang & Morgan N. Price & Allison Hung & Omree Gal-Oz & Surya Tripathi & Christopher W. Smith & Davian Ho & Héloïse Carion & Adam M. Deutschbauer & Adam P. Arkin, 2024. "Barcoded overexpression screens in gut Bacteroidales identify genes with roles in carbon utilization and stress resistance," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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