2K78

Solution Structure of the IsdC NEAT domain bound to Zinc Protoporphyrin

Summary for 2K78

• Entry DOI: 10.2210/pdb2k78/pdb
• NMR Information: BMRB: 15913
• Descriptor: Iron-regulated surface determinant protein C, PROTOPORPHYRIN IX CONTAINING ZN (2 entities in total)
• Functional Keywords: neat domain, nmr complex, heme, isd, isdc, cell wall, iron, metal-binding, peptidoglycan-anchor, secreted, transport protein, heme-binding protein
• Biological source: Staphylococcus aureus (strain MW2)
• Cellular location: Secreted, cell wall; Peptidoglycan-anchor (By similarity): Q7A151
• Total number of polymer chains: 1
• Total formula weight: 17251.47

Authors

Villareal, V.A.,Pilpa, R.M.,Robson, S.A.,Fadeev, E.A.,Clubb, R.T. (deposition date: 2008-08-06, release date: 2008-08-19, Last modification date: 2024-05-22)

Primary citation

Villareal, V.A.,Pilpa, R.M.,Robson, S.A.,Fadeev, E.A.,Clubb, R.T.
The IsdC Protein from Staphylococcus aureus Uses a Flexible Binding Pocket to Capture Heme.
J.Biol.Chem., 283:31591-31600, 2008

PubMed Abstract: Staphylococcus aureus scavenges heme-iron from host hemoproteins using iron-regulated surface determinant (Isd) proteins. IsdC is the central conduit through which heme is passed across the cell wall and binds this molecule using a NEAr Transporter (NEAT) domain. NMR spectroscopy was used to determine the structure of IsdC in complex with a heme analog, zinc-substituted protoporphyrin IX (ZnPPIX). The backbone coordinates of the ensemble of conformers representing the structure exhibit a root mean square deviation to the mean structure of 0.53 +/- 0.11 angstroms. IsdC partially buries protoporphyrin within a large hydrophobic pocket that is located at the end of its beta-barrel structure. The central metal ion of the analog adopts a pentacoordinate geometry in which a highly conserved tyrosine residue serves as a proximal ligand. Consistent with the structure and its role in heme transfer across the cell wall, we show that IsdC weakly binds heme (K(D) = 0.34 +/- 0.12 microm) and that ZnPPIX rapidly dissociates from the protein at a rate of 126 +/- 30 s(-1). NMR studies of the apo-form of IsdC reveal that a 3(10) helix within the binding pocket undergoes a flexible to rigid transition as heme is captured. This structural plasticity may increase the efficiency of heme transfer across the cell wall by facilitating protein-protein interactions between apoIsdC and upstream hemoproteins.

PubMed: 18715872
DOI: 10.1074/jbc.M801126200

Experimental method

SOLUTION NMR