9NHT

Crystal structure of structure of WT BfrB from Pseudomonas aeruginosa in complex with a protein-protein interaction inhibitor KM-5-35

これはPDB形式変換不可エントリーです。

9NHT の概要

• エントリーDOI: 10.2210/pdb9nht/pdb
• 分子名称: Ferroxidase, PROTOPORPHYRIN IX CONTAINING FE, 4-{[(5-bromo-2-hydroxyphenyl)methyl]amino}-1H-isoindole-1,3(2H)-dione, ... (7 entities in total)
• 機能のキーワード: biofilms, electron transport, iron storage, iron binding, iron mobilization, protein-protein interaction inhibitor, oxidoreductase
• 由来する生物種: Pseudomonas aeruginosa PAO1
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 234438.46

構造登録者

Lovell, S.,Seibold, S.,Battaile, K.P.,Yao, H.,Rivera, M. (登録日: 2025-02-25, 公開日: 2025-06-18, 最終更新日: 2025-07-23)

主引用文献

Behm, A.M.,Yao, H.,Eze, E.C.,Alli, S.A.,Baugh, S.D.P.,Ametsetor, E.,Powell, K.M.,Battaile, K.P.,Seibold, S.,Lovell, S.,Bunce, R.A.,Reitz, A.B.,Rivera, M.
Inhibitors of the Bacterioferritin Ferredoxin Complex Dysregulate Iron Homeostasis and Kill Acinetobacter baumannii and Biofilm-Embedded Pseudomonas aeruginosa Cells.
Acs Infect Dis., 11:1983-1993, 2025

PubMed Abstract: In , the iron storage protein bacterioferritin (Bfr) contributes to buffering cytosolic free iron concentrations by oxidizing Fe and storing the resultant Fe in its internal cavity, and by forming a complex with a cognate ferredoxin (Bfd) to reduce the stored Fe and mobilize Fe to the cytosol. Small molecule derivatives of 4-aminoisoindoline-1,3-dione designed to bind Bfr (Pa Bfr) at the Bfd binding site accumulate in the cell, block the Pa Bfr-Bfd complex, inhibit iron mobilization from Pa Bfr, elicit an iron starvation response, are bacteriostatic to planktonic cells, and are bactericidal to biofilm-entrenched cells. A structural alignment of Pa Bfr and Bfr (Ab Bfr) showed strong conservation of the Bfd binding site on Ab Bfr. Accordingly, the small molecule inhibitors of the Pa Bfr-Bfd complex accumulate in the cells, elicit an iron starvation response, are bactericidal to planktonic cells, and exhibit synergy with existing antibiotics. These findings indicate that the inhibition of iron mobilization from Bfr may be an antimicrobial strategy applicable to other Gram-negative pathogens.

PubMed: 40490679
DOI: 10.1021/acsinfecdis.5c00209

実験手法

X-RAY DIFFRACTION (1.85 Å)