View source for 7axn


==14-3-3 sigma in complex with Pin1 binding site pS72 and covalently bound TCF521-026==
<StructureSection load='7axn' size='340' side='right'caption='[[7axn]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7axn]] 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=7AXN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AXN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=S6B:(3-chloranyl-4-imidazol-1-yl-phenyl)methanol'>S6B</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'>[https://proteopedia.org/fgij/fg.htm?mol=7axn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7axn OCA], [https://pdbe.org/7axn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7axn RCSB], [https://www.ebi.ac.uk/pdbsum/7axn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7axn ProSAT]</span></td></tr>
</table>
== Function ==
[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.
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== Publication Abstract from PubMed ==
The stabilization of protein complexes has emerged as a promising modality, expanding the number of entry points for novel therapeutic intervention. Targeting proteins that mediate protein-protein interactions (PPIs), such as hub proteins, is equally challenging and rewarding as they offer an intervention platform for a variety of diseases, due to their large interactome. 14-3-3 hub proteins bind phosphorylated motifs of their interaction partners in a conserved binding channel. The 14-3-3 PPI interface is consequently only diversified by its different interaction partners. Therefore, it is essential to consider, additionally to the potency, also the selectivity of stabilizer molecules. Targeting a lysine residue at the interface of the composite 14-3-3 complex, which can be targeted explicitly via aldimine-forming fragments, we studied the de novo design of PPI stabilizers under consideration of potential selectivity. By applying cooperativity analysis of ternary complex formation, we developed a reversible covalent molecular glue for the 14-3-3/Pin1 interaction. This small fragment led to a more than 250-fold stabilization of the 14-3-3/Pin1 interaction by selective interfacing with a unique tryptophan in Pin1. This study illustrates how cooperative complex formation drives selective PPI stabilization. Further, it highlights how specific interactions within a hub proteins interactome can be stabilized over other interactions with a common binding motif.

Reversible Covalent Imine-Tethering for Selective Stabilization of 14-3-3 Hub Protein Interactions.,Cossar PJ, Wolter M, van Dijck L, Valenti D, Levy LM, Ottmann C, Brunsveld L J Am Chem Soc. 2021 Jun 9;143(22):8454-8464. doi: 10.1021/jacs.1c03035. Epub 2021 , May 28. PMID:34047554<ref>PMID:34047554</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7axn" style="background-color:#fffaf0;"></div>

==See Also==
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dijck Lv]]
[[Category: Ottmann C]]
[[Category: Wolter M]]