View source for 4y32

==Crystal structure of C-terminal modified Tau peptide-hybrid 109B with 14-3-3sigma==
<StructureSection load='4y32' size='340' side='right' caption='[[4y32]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4y32]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y32 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=49F:(2S)-2-(2-METHOXYETHYL)PYRROLIDINE'>49F</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4fl5|4fl5]], [[4y3b|4y3b]], [[4y3v|4y3v]], [[4y5i|4y5i]]</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=4y32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y32 OCA], [http://pdbe.org/4y32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y32 RCSB], [http://www.ebi.ac.uk/pdbsum/4y32 PDBsum]</span></td></tr>
</table>
== 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. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The discovery of novel protein-protein interaction (PPI) modulators represents one of the great molecular challenges of the modern era. PPIs can be modulated by either inhibitor or stabilizer compounds, which target different though proximal regions of the protein interface. In principle, protein-stabilizer complexes can guide the design of PPI inhibitors (and vice versa). In the present work, we combine X-ray crystallographic data from both stabilizer and inhibitor co-crystal complexes of the adapter protein 14-3-3 to characterize, down to the atomic scale, inhibitors of the 14-3-3/Tau PPI, a potential drug target to treat Alzheimer's disease. The most potent compound notably inhibited the binding of phosphorylated full-length Tau to 14-3-3 according to NMR spectroscopy studies. Our work sets a precedent for the rational design of PPI inhibitors guided by PPI stabilizer-protein complexes while potentially enabling access to new synthetically tractable stabilizers of 14-3-3 and other PPIs.

Stabilizer-Guided Inhibition of Protein-Protein Interactions.,Milroy LG, Bartel M, Henen MA, Leysen S, Adriaans JM, Brunsveld L, Landrieu I, Ottmann C Angew Chem Int Ed Engl. 2015 Nov 5. doi: 10.1002/anie.201507976. PMID:26537010<ref>PMID:26537010</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4y32" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bartel, M]]
[[Category: Bier, D]]
[[Category: Brunsveld, L]]
[[Category: Milroy, L]]
[[Category: Ottmann, C]]
[[Category: 14-3-3]]
[[Category: Adapter protein]]
[[Category: Inhibitor]]
[[Category: Peptide binding protein]]
[[Category: Peptide-hybrid]]
[[Category: Protein-protein interaction]]
[[Category: Signaling protein]]