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| | ==Crystal structure of Neutrophil gelatinase-associated lipocalin NGAL (C87S mutant) in complex with fragment 1026, phenylurea== | | ==Crystal structure of Neutrophil gelatinase-associated lipocalin NGAL (C87S mutant) in complex with fragment 1026, phenylurea== |
| - | <StructureSection load='3tzs' size='340' side='right' caption='[[3tzs]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='3tzs' size='340' side='right'caption='[[3tzs]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tzs]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TZS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TZS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tzs]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TZS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TZS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PHU:1-PHENYLUREA'>PHU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PHU:1-PHENYLUREA'>PHU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t1d|3t1d]], [[3tf6|3tf6]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t1d|3t1d]], [[3tf6|3tf6]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNL, LCN2, NGAL, Oncogene 24p3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HNL, LCN2, NGAL, Oncogene 24p3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3tzs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tzs OCA], [http://pdbe.org/3tzs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tzs RCSB], [http://www.ebi.ac.uk/pdbsum/3tzs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tzs 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=3tzs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tzs OCA], [https://pdbe.org/3tzs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tzs RCSB], [https://www.ebi.ac.uk/pdbsum/3tzs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tzs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [[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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Neutrophil gelatinase-associated lipocalin|Neutrophil gelatinase-associated lipocalin]] | | *[[Neutrophil gelatinase-associated lipocalin|Neutrophil gelatinase-associated lipocalin]] |
| - | *[[Siderocalin|Siderocalin]] | + | *[[Siderocalin 3D structures|Siderocalin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Structural genomic]] | | [[Category: Structural genomic]] |
| | [[Category: Apoptosis]] | | [[Category: Apoptosis]] |
| Structural highlights
3tzs is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | |
| Gene: | HNL, LCN2, NGAL, Oncogene 24p3 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[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.[1]
Publication Abstract from PubMed
Siderocalin (also lipocalin 2, NGAL or 24p3) binds iron as complexes with specific siderophores, which are low molecular weight, ferric ion-specific chelators. In innate immunity, siderocalin slows the growth of infecting bacteria by sequestering bacterial ferric siderophores. Siderocalin also binds simple catechols, which can serve as siderophores in the damaged urinary tract. Siderocalin has also been proposed to alter cellular iron trafficking, for instance, driving apoptosis through iron efflux via BOCT. An endogenous siderophore composed of gentisic acid (2,5-dihydroxybenzoic acid) substituents was proposed to mediate cellular efflux. However, binding studies reported herein contradict the proposal that gentisic acid forms high-affinity ternary complexes with siderocalin and iron, or that gentisic acid can serve as an endogenous siderophore at neutral pH. We also demonstrate that siderocalin does not induce cellular iron efflux or stimulate apoptosis, questioning the role siderocalin plays in modulating iron metabolism.
Siderocalin/Lcn2/NGAL/24p3 does not drive apoptosis through gentisic acid mediated iron withdrawal in hematopoietic cell lines.,Correnti C, Richardson V, Sia AK, Bandaranayake AD, Ruiz M, Suryo Rahmanto Y, Kovacevic Z, Clifton MC, Holmes MA, Kaiser BK, Barasch J, Raymond KN, Richardson DR, Strong RK PLoS One. 2012;7(8):e43696. doi: 10.1371/journal.pone.0043696. Epub 2012 Aug 21. PMID:22928018[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J. An iron delivery pathway mediated by a lipocalin. Mol Cell. 2002 Nov;10(5):1045-56. PMID:12453413
- ↑ Correnti C, Richardson V, Sia AK, Bandaranayake AD, Ruiz M, Suryo Rahmanto Y, Kovacevic Z, Clifton MC, Holmes MA, Kaiser BK, Barasch J, Raymond KN, Richardson DR, Strong RK. Siderocalin/Lcn2/NGAL/24p3 does not drive apoptosis through gentisic acid mediated iron withdrawal in hematopoietic cell lines. PLoS One. 2012;7(8):e43696. doi: 10.1371/journal.pone.0043696. Epub 2012 Aug 21. PMID:22928018 doi:http://dx.doi.org/10.1371/journal.pone.0043696
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