Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH

Pathogens must steal iron from their hosts to establish infection. In mammals, hemoglobin (Hb) represents the largest reservoir of iron, and pathogens express Hb-binding proteins to access this source. Here, we show how one of the commonest and most significant human pathogens, Staphylococcus aureus, captures Hb as the first step of an iron-scavenging pathway. The x-ray crystal structure of Hb bound to a domain from the Isd (iron-regulated surface determinant) protein, IsdH, is the first structure of a Hb capture complex to be determined. Surface mutations in Hb that reduce binding to the Hb-receptor limit the capacity of S. aureus to utilize Hb as an iron source, suggesting that Hb sequence is a factor in host susceptibility to infection. The demonstration that pathogens make highly specific recognition complexes with Hb raises the possibility of developing inhibitors of Hb binding as antibacterial agents. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Structure of the hemoglobin-isdh complex reveals the molecular basis of iron capture by staphylococcus aureus

Background: IsdB and IsdH proteins from Staphylococcus aureus strip heme iron from human hemoglobin. Results: The IsdH·hemoglobin complex shows how globin-binding and heme-binding NEAT domains of IsdH cooperate to remove heme from both chains of hemoglobin. Conclusion: The supradomain architecture of IsdH confers activity by precisely positioning the heme acceptor domain. Significance: Multiple IsdH·hemoglobin interfaces may be targets for new antibiotics. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc