7E1S

Crystal structure of dehydrogenase/isomerase FabX from Helicobacter pylori in complex with octanoyl-ACP

7E1S の概要

• エントリーDOI: 10.2210/pdb7e1s/pdb
• 分子名称: 2-nitropropane dioxygenase, Acyl carrier protein,Acyl carrier protein, FLAVIN MONONUCLEOTIDE, ... (6 entities in total)
• 機能のキーワード: unsaturated fatty acid biosynthesis, fmn, 4fe-4s cluster, flavoprotein
• 由来する生物種: Helicobacter pylori; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 103054.72

構造登録者

Zhou, J.S.,Zhang, L.,Zhang, L. (登録日: 2021-02-03, 公開日: 2021-12-01, 最終更新日: 2024-11-13)

主引用文献

Zhou, J.,Zhang, L.,Zeng, L.,Yu, L.,Duan, Y.,Shen, S.,Hu, J.,Zhang, P.,Song, W.,Ruan, X.,Jiang, J.,Zhang, Y.,Zhou, L.,Jia, J.,Hang, X.,Tian, C.,Lin, H.,Chen, H.Z.,Cronan, J.E.,Bi, H.,Zhang, L.
Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis.
Nat Commun, 12:6932-6932, 2021

PubMed 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.

PubMed: 34836944
DOI: 10.1038/s41467-021-27148-0

実験手法

X-RAY DIFFRACTION (2.31 Å)