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| | <StructureSection load='5mxo' size='340' side='right'caption='[[5mxo]], [[Resolution|resolution]] 1.20Å' scene=''> | | <StructureSection load='5mxo' size='340' side='right'caption='[[5mxo]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mxo]] is a 2 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=5MXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MXO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mxo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MXO 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=FSC:FUSICOCCIN'>FSC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=FSC:FUSICOCCIN'>FSC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5mxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mxo OCA], [https://pdbe.org/5mxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mxo RCSB], [https://www.ebi.ac.uk/pdbsum/5mxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mxo ProSAT]</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=5mxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mxo OCA], [http://pdbe.org/5mxo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mxo RCSB], [http://www.ebi.ac.uk/pdbsum/5mxo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mxo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. | + | [https://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andrei, S]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Leysen, S]] | + | [[Category: Andrei S]] |
| - | [[Category: Ottmann, C]] | + | [[Category: Leysen S]] |
| - | [[Category: 14-3-3 p53 fusicoccin antitumor protein]] | + | [[Category: Ottmann C]] |
| - | [[Category: Antitumor protein]]
| + | |
| Structural highlights
Function
1433S_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
Publication Abstract from PubMed
14-3-3 proteins are positive regulators of the tumor suppressor p53, the mutation of which is implicated in many human cancers. Current strategies for targeting of p53 involve restoration of wild-type function or inhibition of the interaction with MDM2, its key negative regulator. Despite the efficacy of these strategies, the alternate approach of stabilizing the interaction of p53 with positive regulators and, thus, enhancing tumor suppressor activity, has not been explored. Here, we report the first example of small-molecule stabilization of the 14-3-3 - p53 protein-protein interaction (PPI) and demonstrate the potential of this approach as a therapeutic modality. We also observed a disconnect between biophysical and crystallographic data in the presence of a stabilizing molecule, which is unusual in 14-3-3 PPIs.
Small-molecule stabilization of the p53 - 14-3-3 protein-protein interaction.,Doveston RG, Kuusk A, Andrei SA, Leysen S, Cao Q, Castaldi MP, Hendricks A, Brunsveld L, Chen H, Boyd H, Ottmann C FEBS Lett. 2017 Aug;591(16):2449-2457. doi: 10.1002/1873-3468.12723. Epub 2017, Aug 6. PMID:28640363[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Doveston RG, Kuusk A, Andrei SA, Leysen S, Cao Q, Castaldi MP, Hendricks A, Brunsveld L, Chen H, Boyd H, Ottmann C. Small-molecule stabilization of the p53 - 14-3-3 protein-protein interaction. FEBS Lett. 2017 Aug;591(16):2449-2457. doi: 10.1002/1873-3468.12723. Epub 2017, Aug 6. PMID:28640363 doi:http://dx.doi.org/10.1002/1873-3468.12723
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