9LT7

Crystal structure of dehydrogenase/isomerase FabX from Helicobacter pylori in complex with inhibitor 11

これはPDB形式変換不可エントリーです。

9LT7 の概要

• エントリーDOI: 10.2210/pdb9lt7/pdb
• 分子名称: 2-nitropropane dioxygenase, FLAVIN MONONUCLEOTIDE, IRON/SULFUR CLUSTER, ... (5 entities in total)
• 機能のキーワード: fatty acid synthesis; dehydrogenase; isomerase; fabx, biosynthetic protein
• 由来する生物種: Helicobacter pylori
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40910.32

構造登録者

zhang, L.,Zhang, L. (登録日: 2025-02-06, 公開日: 2025-12-24)

主引用文献

Ruan, X.,Zhang, L.,Dong, L.,Wang, Y.,Zeng, L.,Yang, M.,Bi, H.,Feng, M.,Zhang, L.,Zhou, L.
Discovery of 1,3,4-Thiadiazole Sulfonamide-Based Potent Inhibitors against the Unsaturated Fatty Acid Synthase FabX of Helicobacter pylori.
J.Med.Chem., 68:17175-17188, 2025

PubMed Abstract: Unsaturated fatty acids (UFAs) are essential for the membrane function in most bacteria. In (), a gastric pathogen, UFA biosynthesis depends on the bifunctional dehydrogenase/isomerase FabX, a promising target against . Herein, we report the first FabX inhibitor, (compound , IC = 3.7 ± 0.2 μM), identified via high-throughput screening and featuring a 1,3,4-thiadiazole sulfonamide scaffold. The costructure of FabX- reveals occupancy of the L-shaped substrate-binding tunnel via hydrophobic interactions and hydrogen bonds. Structure-based optimization led to more potent derivatives, among which compound showed potent inhibition (IC = 0.128 ± 0.002 μM), representing a 29-fold improvement. Compound also demonstrated strong antibacterial activity (MIC = 0.5-1 μg/mL), when combined with membrane permeabilizers, efflux pump inhibitors, and clarithromycin, and exhibited narrow-spectrum efficacy against , providing a novel strategy for anti- therapy.

PubMed: 40811148
DOI: 10.1021/acs.jmedchem.5c00654

実験手法

X-RAY DIFFRACTION (1.6 Å)