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Structural Basis for Hemoglobin Capture by Staphylococcus aureus Cell-surface Protein, IsdH

  作者 Kumar, KK; Jacques, DA; Pishchany, G; Caradoc-Davies, T; Spirig, T; Malmirchegini, GR; Langley, DB; Dickson, CF; Mackay, JP; Clubb, RT; Skaar, EP; Guss, JM; Gell, DA  
  选自 期刊  Journal of Biological Chemistry;  卷期  2011年286-44;  页码  38439-38447  
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[摘要]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.

 
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