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| | ==Solution Structure of the IsdC NEAT domain bound to Zinc Protoporphyrin== | | ==Solution Structure of the IsdC NEAT domain bound to Zinc Protoporphyrin== |
| - | <StructureSection load='2k78' size='340' side='right' caption='[[2k78]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''> | + | <StructureSection load='2k78' size='340' side='right'caption='[[2k78]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k78]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Staaw Staaw]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K78 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K78 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k78]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staaw Staaw]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K78 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZNH:PROTOPORPHYRIN+IX+CONTAINING+ZN'>ZNH</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZNH:PROTOPORPHYRIN+IX+CONTAINING+ZN'>ZNH</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">isdC, sirD, MW1013 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=196620 STAAW])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">isdC, sirD, MW1013 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=196620 STAAW])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k78 OCA], [http://pdbe.org/2k78 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k78 RCSB], [http://www.ebi.ac.uk/pdbsum/2k78 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2k78 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k78 OCA], [https://pdbe.org/2k78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k78 RCSB], [https://www.ebi.ac.uk/pdbsum/2k78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k78 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ISDC_STAAW 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.<ref>PMID:18184657</ref> | + | [[https://www.uniprot.org/uniprot/ISDC_STAAW 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.<ref>PMID:18184657</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Staaw]] | | [[Category: Staaw]] |
| | [[Category: Clubb, R T]] | | [[Category: Clubb, R T]] |
| Structural highlights
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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu M, Tanaka WN, Zhu H, Xie G, Dooley DM, Lei B. Direct hemin transfer from IsdA to IsdC in the iron-regulated surface determinant (Isd) heme acquisition system of Staphylococcus aureus. J Biol Chem. 2008 Mar 14;283(11):6668-76. doi: 10.1074/jbc.M708372200. Epub 2008 , Jan 9. PMID:18184657 doi:http://dx.doi.org/10.1074/jbc.M708372200
- ↑ Villareal VA, Pilpa RM, Robson SA, Fadeev EA, Clubb RT. The IsdC protein from Staphylococcus aureus uses a flexible binding pocket to capture heme. J Biol Chem. 2008 Nov 14;283(46):31591-600. Epub 2008 Aug 20. PMID:18715872 doi:10.1074/jbc.M801126200
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