7K5H

1.90 A resolution structure of WT BfrB from Pseudomonas aeruginosa in complex with a protein-protein interaction inhibitor KM-5-66

Summary for 7K5H

• Entry DOI: 10.2210/pdb7k5h/pdb
• Descriptor: Ferroxidase, POTASSIUM ION, PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total)
• Functional Keywords: biofilms, electron transport, iron storage, iron binding, iron mobilization, protein-protein interaction inhibitor, oxidoreductase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 12
• Total formula weight: 231033.14

Authors

Lovell, S.,Battaile, K.P.,Soldano, A.,Punchi-Hewage, A.,Meraz, K.,Annor-Gyamfi, J.K.,Yao, H.,Bunce, R.A.,Rivera, M. (deposition date: 2020-09-16, release date: 2020-12-16, Last modification date: 2023-10-18)

Primary citation

Soldano, A.,Yao, H.,Punchi Hewage, A.N.D.,Meraz, K.,Annor-Gyamfi, J.K.,Bunce, R.A.,Battaile, K.P.,Lovell, S.,Rivera, M.
Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas aeruginosa Cells.
Acs Infect Dis., 7:123-140, 2021

PubMed Abstract: Bacteria depend on a well-regulated iron homeostasis to survive adverse environments. A key component of the iron homeostasis machinery is the compartmentalization of Fe in bacterioferritin and its subsequent mobilization as Fe to satisfy metabolic requirements. In Fe is compartmentalized in bacterioferritin (BfrB), and its mobilization to the cytosol requires binding of a ferredoxin (Bfd) to reduce the stored Fe and release the soluble Fe. Blocking the BfrB-Bfd complex in by deletion of the gene triggers an irreversible accumulation of Fe in BfrB, concomitant cytosolic iron deficiency and significant impairment of biofilm development. Herein we report that small molecules developed to bind BfrB at the Bfd binding site block the BfrB-Bfd complex, inhibit the mobilization of iron from BfrB in cells, elicit a bacteriostatic effect on planktonic cells, and are bactericidal to cells embedded in mature biofilms.

PubMed: 33269912
DOI: 10.1021/acsinfecdis.0c00669

Experimental method

X-RAY DIFFRACTION (1.9 Å)