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| | ==Solution structure of S100A13 with a drug amlexanox== | | ==Solution structure of S100A13 with a drug amlexanox== |
| - | <StructureSection load='2kot' size='340' side='right' caption='[[2kot]], [[NMR_Ensembles_of_Models | 18 NMR models]]' scene=''> | + | <StructureSection load='2kot' size='340' side='right'caption='[[2kot]], [[NMR_Ensembles_of_Models | 18 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kot]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KOT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kot]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KOT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANW:2-AMINO-7-(1-METHYLETHYL)-5-OXO-5H-CHROMENO[2,3-B]PYRIDINE-3-CARBOXYLIC+ACID'>ANW</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANW:2-AMINO-7-(1-METHYLETHYL)-5-OXO-5H-CHROMENO[2,3-B]PYRIDINE-3-CARBOXYLIC+ACID'>ANW</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S100A13 ([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">S100A13 ([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=2kot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kot OCA], [http://pdbe.org/2kot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kot RCSB], [http://www.ebi.ac.uk/pdbsum/2kot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kot 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=2kot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kot OCA], [https://pdbe.org/2kot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kot RCSB], [https://www.ebi.ac.uk/pdbsum/2kot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kot ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/S10AD_HUMAN S10AD_HUMAN]] Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine (By similarity).<ref>PMID:12746488</ref> <ref>PMID:20863990</ref> | + | [[https://www.uniprot.org/uniprot/S10AD_HUMAN S10AD_HUMAN]] Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine (By similarity).<ref>PMID:12746488</ref> <ref>PMID:20863990</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[S100 protein|S100 protein]] | + | *[[S100 proteins 3D structures|S100 proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Mohan, S K]] | | [[Category: Mohan, S K]] |
| | [[Category: Rani, S G]] | | [[Category: Rani, S G]] |
| Structural highlights
Function
[S10AD_HUMAN] Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine (By similarity).[1] [2]
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
S100A13 and acidic fibroblast growth factor (FGF1) are involved in a wide array of important biological processes, such as angiogenesis, cell differentiation, neurogenesis, and tumor growth. Generally, the biological function of FGF1 is to recognize a specific tyrosine kinase on the cell surface and initiate the cell signal transduction cascade. Amlexanox (2-amino-7-isopropyl-5-oxo-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylic acid) is an antiallergic drug that binds S100A13 and FGF1 and inhibits the heat shock induced release of S100A13 and FGF1. In the present study, we investigated the interaction of amlexanox with S100A13 using various biophysical techniques, including isothermal titration calorimetry, fluorescence spectrophotometry, and multidimensional NMR spectroscopy. We report the three-dimensional solution structure of the S100A13-amlexanox complex. These data show that amlexanox binds specifically to the FGF1-S100A13 interface and prevents the formation of the FGF1-releasing complex. In addition, we demonstrate that amlexanox acts as an antagonist of S100A13 by binding to its FGF1 binding site and subsequently inhibiting the nonclassical pathway of these proteins. This inhibition likely results in the ability of amlexanox to antagonize the angiogenic and mitogenic activity of FGF1.
Molecular Level Interactions of S100A13 with Amlexanox: Inhibitor for Formation of the Multiprotein Complex in the Nonclassical Pathway of Acidic Fibroblast Growth Factor.,Rani SG, Mohan SK, Yu C Biochemistry. 2010 Mar 2. PMID:20178375[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mandinova A, Soldi R, Graziani I, Bagala C, Bellum S, Landriscina M, Tarantini F, Prudovsky I, Maciag T. S100A13 mediates the copper-dependent stress-induced release of IL-1alpha from both human U937 and murine NIH 3T3 cells. J Cell Sci. 2003 Jul 1;116(Pt 13):2687-96. Epub 2003 May 13. PMID:12746488 doi:http://dx.doi.org/10.1242/jcs.00471
- ↑ Cao R, Yan B, Yang H, Zu X, Wen G, Zhong J. Effect of human S100A13 gene silencing on FGF-1 transportation in human endothelial cells. J Formos Med Assoc. 2010 Sep;109(9):632-40. doi: 10.1016/S0929-6646(10)60103-9. PMID:20863990 doi:http://dx.doi.org/10.1016/S0929-6646(10)60103-9
- ↑ Rani SG, Mohan SK, Yu C. Molecular Level Interactions of S100A13 with Amlexanox: Inhibitor for Formation of the Multiprotein Complex in the Nonclassical Pathway of Acidic Fibroblast Growth Factor. Biochemistry. 2010 Mar 2. PMID:20178375 doi:10.1021/bi9019077
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