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PDBsum entry 7k5h
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Oxidoreductase
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PDB id
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7k5h
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References listed in PDB file
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Key reference
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Title
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Small molecule inhibitors of the bacterioferritin (bfrb)-Ferredoxin (bfd) complex kill biofilm-Embedded pseudomonas aeruginosa cells.
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Authors
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A.Soldano,
H.Yao,
A.N.D.Punchi hewage,
K.Meraz,
J.K.Annor-Gyamfi,
R.A.Bunce,
K.P.Battaile,
S.Lovell,
M.Rivera.
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Ref.
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ACS Infect Dis, 2021,
7,
123-140.
[DOI no: ]
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PubMed id
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Abstract
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Bacteria depend on a well-regulated iron homeostasis to survive adverse
environments. A key component of the iron homeostasis machinery is the
compartmentalization of Fe3+ in bacterioferritin and its subsequent
mobilization as Fe2+ to satisfy metabolic requirements. In
Pseudomonas aeruginosa Fe3+ is compartmentalized in
bacterioferritin (BfrB), and its mobilization to the cytosol requires binding of
a ferredoxin (Bfd) to reduce the stored Fe3+ and release the soluble
Fe2+. Blocking the BfrB-Bfd complex in P. aeruginosa by
deletion of the bfd gene triggers an irreversible accumulation of
Fe3+ 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 P. aeruginosa cells,
elicit a bacteriostatic effect on planktonic cells, and are bactericidal to
cells embedded in mature biofilms.
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