View source for 1x89


==Crystal structure of Siderocalin (NGAL, Lipocalin 2) complexed with Carboxymycobactin S==
<StructureSection load='1x89' size='340' side='right'caption='[[1x89]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1x89]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X89 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CM1:CARBOXYMYCOBACTIN+S'>CM1</scene></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=1x89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x89 OCA], [https://pdbe.org/1x89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x89 RCSB], [https://www.ebi.ac.uk/pdbsum/1x89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x89 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NGAL_HUMAN NGAL_HUMAN] Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity, possibly by sequestrating iron, leading to limit bacterial growth.<ref>PMID:12453413</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/x8/1x89_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1x89 ConSurf].
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== Publication Abstract from PubMed ==
Siderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels in serum and synovium during bacterial infection; it is also secreted from epithelial cells in response to inflammation or tumorigenesis. Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes. Supporting this hypothesis, siderocalin is a potent bacteriostatic agent in vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible to bacterial infection. Here we show that siderocalin also binds soluble siderophores of mycobacteria, including M. tuberculosis: carboxymycobactins. Siderocalin employs a degenerate recognition mechanism to cross react with these dissimilar types of siderophores, broadening the potential utility of this innate immune defense.

Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration.,Holmes MA, Paulsene W, Jide X, Ratledge C, Strong RK Structure. 2005 Jan;13(1):29-41. PMID:15642259<ref>PMID:15642259</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1x89" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neutrophil gelatinase-associated lipocalin|Neutrophil gelatinase-associated lipocalin]]
*[[Siderocalin|Siderocalin]]
*[[Siderocalin 3D structures|Siderocalin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Holmes MA]]
[[Category: Jide X]]
[[Category: Paulsene W]]
[[Category: Ratledge C]]
[[Category: Strong RK]]