3SZK

Crystal Structure of Human metHaemoglobin Complexed with the First NEAT Domain of IsdH from Staphylococcus aureus

Summary for 3SZK

• Entry DOI: 10.2210/pdb3szk/pdb
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, Iron-regulated surface determinant protein H, ... (4 entities in total)
• Functional Keywords: methaemoglobin, neat domain, isdh, host-pathogen interaction, oxygen transport-protein binding complex, oxygen transport/protein binding
• Biological source: Staphylococcus aureus; More
• Cellular location: Secreted, cell wall; Peptidoglycan-anchor (Potential): Q8NW39
• Total number of polymer chains: 6
• Total formula weight: 102356.70

Authors

Jacques, D.A.,Kumar, K.K.,Guss, J.M.,Gell, D.A. (deposition date: 2011-07-19, release date: 2011-09-14, Last modification date: 2023-11-01)

Primary citation

Krishna Kumar, K.,Jacques, D.A.,Pishchany, G.,Caradoc-Davies, T.,Spirig, T.,Malmirchegini, G.R.,Langley, D.B.,Dickson, C.F.,Mackay, J.P.,Clubb, R.T.,Skaar, E.P.,Guss, J.M.,Gell, D.A.
Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH
J.Biol.Chem., 286:38439-38447, 2011

PubMed Abstract: 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.

PubMed: 21917915
DOI: 10.1074/jbc.M111.287300

Experimental method

X-RAY DIFFRACTION (3.01 Å)