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2kot

From Proteopedia

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Revision as of 08:10, 25 July 2018

Solution structure of S100A13 with a drug amlexanox

Structural highlights

2kot is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	S100A13 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kot"

@@ Line 1: / Line 1: @@
 ==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=''>
@@ Line 5: / Line 6: @@
 </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>
 <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='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]</span></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>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ko/2kot_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ko/2kot_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 39: / Line 40: @@
 [[Category: Rani, S G]]
 [[Category: Yu, C]]
+[[Category: Calcium]]
 [[Category: Phosphoprotein]]
 [[Category: S100a13]]
 [[Category: Signaling protein]]

2kot

From Proteopedia

Revision as of 08:10, 25 July 2018

Solution structure of S100A13 with a drug amlexanox

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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