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| | <StructureSection load='5n75' size='340' side='right'caption='[[5n75]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='5n75' size='340' side='right'caption='[[5n75]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5n75]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N75 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5N75 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5n75]] is a 2 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=5N75 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N75 FirstGlance]. <br> |
| - | </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=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]] 1.803Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5n75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n75 OCA], [http://pdbe.org/5n75 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n75 RCSB], [http://www.ebi.ac.uk/pdbsum/5n75 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n75 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=5n75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n75 OCA], [https://pdbe.org/5n75 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n75 RCSB], [https://www.ebi.ac.uk/pdbsum/5n75 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n75 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: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Leysen, S]] | + | [[Category: Leysen S]] |
| - | [[Category: Ottmann, C]] | + | [[Category: Ottmann C]] |
| - | [[Category: Sijbesma, E]] | + | [[Category: Sijbesma E]] |
| - | [[Category: 14-3-3]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Taz]]
| + | |
| - | [[Category: Yap]]
| + | |
| 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
Proteins typically interact with multiple binding partners, and often different parts of their surfaces are employed to establish these protein-protein interactions (PPIs). Members of the class of 14-3-3 adapter proteins bind to several hundred other proteins in the cell. Multiple small molecules for the modulation of 14-3-3 PPIs have been disclosed; however, they all target the conserved phosphopeptide binding channel, so that selectivity is difficult to achieve. Here we report on the discovery of two individual secondary binding sites that have been identified by combining nuclear magnetic resonance-based fragment screening and X-ray crystallography. The two pockets that these fragments occupy are part of at least three physiologically relevant and structurally characterized 14-3-3 PPI interfaces, including those with serotonin N-acetyltransferase and plant transcription factor FT. In addition, the high degree of conservation of the two sites implies their relevance for 14-3-3 PPIs. This first identification of secondary sites on 14-3-3 proteins bound by small molecule ligands might facilitate the development of new chemical tool compounds for more selective PPI modulation.
Identification of Two Secondary Ligand Binding Sites in 14-3-3 Proteins Using Fragment Screening.,Sijbesma E, Skora L, Leysen S, Brunsveld L, Koch U, Nussbaumer P, Jahnke W, Ottmann C Biochemistry. 2017 Aug 1;56(30):3972-3982. doi: 10.1021/acs.biochem.7b00153. Epub, 2017 Jul 21. PMID:28681606[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sijbesma E, Skora L, Leysen S, Brunsveld L, Koch U, Nussbaumer P, Jahnke W, Ottmann C. Identification of Two Secondary Ligand Binding Sites in 14-3-3 Proteins Using Fragment Screening. Biochemistry. 2017 Aug 1;56(30):3972-3982. doi: 10.1021/acs.biochem.7b00153. Epub, 2017 Jul 21. PMID:28681606 doi:http://dx.doi.org/10.1021/acs.biochem.7b00153
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