2k78

Solution Structure of the IsdC NEAT domain bound to Zinc Protoporphyrin

spinqualitylabelsall models 2k78 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2k78 is a 1 chain structure with sequence from Staphylococcus aureus subsp. aureus MW2. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: ZNH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ISDC_STAAW Involved in heme (porphyrin) scavenging. Binds hemoglobin and almost exclusively free-base protoporphyrin IX. Probably has a role as the central conduit of the isd heme uptake system, i.e. mediates the transfer of the iron-containing nutrient from IsdABH to the membrane translocation system IsdDEF (By similarity). Hemin-free IsdC (apo-IsdC) acquires hemin from hemin-containing IsdA (holo-IsdA) probably through the activated holo-IsdA-apo-IsdC complex and due to the higher affinity of apo-IsdC for the cofactor. The reaction is reversible. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. The IsdC protein from Staphylococcus aureus uses a flexible binding pocket to capture heme.,Villareal VA, Pilpa RM, Robson SA, Fadeev EA, Clubb RT J Biol Chem. 2008 Nov 14;283(46):31591-600. Epub 2008 Aug 20. PMID:18715872 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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