View source for 2ite


==Crystal structure of the IsdA NEAT domain from Staphylococcus aureus==
<StructureSection load='2ite' size='340' side='right'caption='[[2ite]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ite]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ITE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ITE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2itf|2itf]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">isdA, frpA, stbA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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=2ite FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ite OCA], [https://pdbe.org/2ite PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ite RCSB], [https://www.ebi.ac.uk/pdbsum/2ite PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ite ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/ISDA_STAAW ISDA_STAAW]] Transfers its hemin to hemin-free IsdC (apo-IsdC) directly probably through the activated holo-IsdA-apo-IsdC complex and driven by the higher affinity of apo-IsdC for the cofactor. The reaction is reversible. Binds transferrin, lactoferrin, heme, hemoglobin, hemin, fetuin, asialofetuin and protein A. Also binds fibronectin and chains B-beta and gamma of fibrinogen. Could play a role in the removal of heme from hemoglobin. The IsdA-mediated iron-acquisition system from transferrin could play only an ancillary role in the iron uptake whereas the siderophore-mediated iron-acquisition system from transferrin seems to play an essential or dominant role. May function as a reservoir for heme. Involved in adherence of S.aureus to human desquamated nasal epithelial cells and is required for nasal colonization. Protects S.aureus against the bactericidal protease activity of apolactoferrin in vitro and confers resistance to bovine lactoferricin (By similarity). Also IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils.<ref>PMID:18097052</ref> <ref>PMID:18184657</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/it/2ite_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ite ConSurf].
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== Publication Abstract from PubMed ==
Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as the sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains.

Haem recognition by a Staphylococcus aureus NEAT domain.,Grigg JC, Vermeiren CL, Heinrichs DE, Murphy ME Mol Microbiol. 2007 Jan;63(1):139-49. PMID:17229211<ref>PMID:17229211</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Grigg, J C]]
[[Category: Heinrichs, D E]]
[[Category: Murphy, M E]]
[[Category: Vermeiren, C L]]
[[Category: Heme]]
[[Category: Iron]]
[[Category: Metal binding protein]]
[[Category: Neat domain]]