9F95

Complex of phenazine biosynthesis enzyme PhzF with 2-amino-3-hydroxy-5-(3-hydroxyphenyl)benzoic acid

これはPDB形式変換不可エントリーです。

9F95 の概要

• エントリーDOI: 10.2210/pdb9f95/pdb
• 関連するPDBエントリー: 9F92 9F93 9F94 9F96
• 分子名称: Trans-2,3-dihydro-3-hydroxyanthranilate isomerase, 2-azanyl-5-(3-hydroxyphenyl)-3-oxidanyl-benzoic acid (3 entities in total)
• 機能のキーワード: inhibitor, complex, phenazine biosynthesis, pyocyanin, isomerase
• 由来する生物種: Pseudomonas fluorescens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32501.79

構造登録者

Baumgarten, J.,Schneider, P.,Blankenfeldt, W.,Kunick, C. (登録日: 2024-05-07, 公開日: 2024-10-09, 最終更新日: 2025-01-01)

主引用文献

Baumgarten, J.,Schneider, P.,Thiemann, M.,Zimmermann, M.,Diederich, C.,Blankenfeldt, W.,Kunick, C.
Substrate-Based Ligand Design for Phenazine Biosynthesis Enzyme PhzF.
Chemmedchem, 19:e202400466-e202400466, 2024

PubMed Abstract: The phenazine pyocyanin is an important virulence factor of the pathogen Pseudomonas aeruginosa, which is on the WHO list of antibiotic resistant "priority pathogens". In this study the isomerase PhzF, a key bacterial enzyme of the pyocyanin biosynthetic pathway, was investigated as a pathoblocker target. The aim of the pathoblocker strategy is to reduce the virulence of the pathogen without killing it, thus preventing the rapid development of resistance. Based on crystal structures of PhzF, derivatives of the inhibitor 3-hydroxyanthranilic acid were designed. Co-crystal structures of the synthesized derivatives with PhzF revealed spacial limitations of the binding pocket of PhzF in the closed conformation. In contrast, ligands aligned to the open conformation of PhzF provided more room for structural modifications. The intrinsic fluorescence of small 3-hydroxyanthranilic acid derivatives enabled direct affinity determinations using FRET assays. The analysis of structure-activity relationships showed that the carboxylic acid moiety is essential for binding to the target enzyme. The results of this study provide fundamental structural insights that will be useful for the design of PhzF-inhibitors.

PubMed: 39163032
DOI: 10.1002/cmdc.202400466

実験手法

X-RAY DIFFRACTION (1.46 Å)