Structural Analysis and Inhibitor Modeling of Bacterioferritin From Brucella abortus

ABSTRACT Iron homeostasis in various pathogenic bacteria is regulated by bacterioferritins (Bfr) which function to store Fe 3+ and release Fe 2+ as needed for metabolic processes. The Bfr structure consists of 18 kDa subunits in which dimer pairs bind a heme molecule and are assembled into a highly symmetrical 24‐meric spherical structure with an internal core diameter of approximately 80 Å. Release of iron is facilitated by the binding of a 7 kDa [2Fe‐2S] ferredoxin (Bfd) to specific sites on the surface of Bfr which transfers electrons to the core thereby reducing the stored Fe 3+ to Fe 2+ for mobilization. The crystal structures of Bfr from Brucella abortus ( Ba ) in the apo and iron bound forms are presented and compared with those from Acinetobacter baumannii ( Ab ) and Pseudomonas aeruginosa ( Pa ). Additionally, models of the Bfr:Bfd complexes for Ba and Ab are provided and compared with the Pa complex. Finally, compounds known to target the Bfr:Bfd interaction in Pa were docked to the Ba and Ab structures which provided insight regarding the potential binding mode and inhibitory mechanism.