View source for 6qds


==Crystal structure of 14-3-3sigma in complex with a PAK6 pT99 phosphopeptide stabilized by semi-synthetic fusicoccane FC-NCPC==
<StructureSection load='6qds' size='340' side='right'caption='[[6qds]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qds]] 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=6QDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QDS 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]] 1.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HY5:~{N}-[(2~{S})-2-[(1~{E},3~{R},4~{S},8~{R},9~{R},10~{R},11~{S},14~{S})-14-(methoxymethyl)-3,10-dimethyl-8-[(2~{S},3~{R},4~{S},5~{S},6~{R})-6-(2-methylbut-3-en-2-yloxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-4,9-bis(oxidanyl)-6-tricyclo[9.3.0.0^{3,7}]tetradeca-1,6-dienyl]propyl]cyclopropanecarboxamide'>HY5</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=6qds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qds OCA], [https://pdbe.org/6qds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qds RCSB], [https://www.ebi.ac.uk/pdbsum/6qds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qds 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 ==
Targeting protein-protein interactions (PPIs) is a promising approach in the development of drugs for many indications. 14-3-3 proteins are a family of phosphoprotein-binding molecules with critical functions in dozens of cell signaling networks. 14-3-3s are abundant in the central nervous system, and the small molecule fusicoccin-A (FC-A), a tool compound that can be used to manipulate 14-3-3 PPIs, enhances neurite outgrowth in cultured neurons. New semisynthetic FC-A derivatives with improved binding affinity for 14-3-3 complexes have recently been developed. Here, we use a series of screens that identify these compounds as potent inducers of neurite outgrowth through a polypharmacological mechanism. Using proteomics and X-ray crystallography, we discover that these compounds extensively regulate the 14-3-3 interactome by stabilizing specific PPIs, while disrupting others. These results provide new insights into the development of drugs to target 14-3-3 PPIs, a potential therapeutic strategy for CNS diseases.

Polypharmacological Perturbation of the 14-3-3 Adaptor Protein Interactome Stimulates Neurite Outgrowth.,Kaplan A, Andrei SA, van Regteren Altena A, Simas T, Banerjee SL, Kato N, Bisson N, Higuchi Y, Ottmann C, Fournier AE Cell Chem Biol. 2020 Jun 18;27(6):657-667.e6. doi:, 10.1016/j.chembiol.2020.02.010. Epub 2020 Mar 26. PMID:32220335<ref>PMID:32220335</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qds" 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: Andrei SA]]
[[Category: Fournier AE]]
[[Category: Kaplan A]]
[[Category: Ottman C]]