6qdu
From Proteopedia
(Difference between revisions)
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==Crystal structure of 14-3-3sigma in complex with a RapGef2 pT740 phosphopeptide inhibited by semi-synthetic fusicoccane FC-NCPC== | ==Crystal structure of 14-3-3sigma in complex with a RapGef2 pT740 phosphopeptide inhibited by semi-synthetic fusicoccane FC-NCPC== | ||
| - | <StructureSection load='6qdu' size='340' side='right'caption='[[6qdu]]' scene=''> | + | <StructureSection load='6qdu' size='340' side='right'caption='[[6qdu]], [[Resolution|resolution]] 1.63Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QDU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qdu]] is a 1 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=6QDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QDU FirstGlance]. <br> |
| - | </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=6qdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qdu OCA], [https://pdbe.org/6qdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qdu RCSB], [https://www.ebi.ac.uk/pdbsum/6qdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qdu ProSAT]</span></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]] 1.632Å</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=HY5:FC-NCPC'>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=6qdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qdu OCA], [https://pdbe.org/6qdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qdu RCSB], [https://www.ebi.ac.uk/pdbsum/6qdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qdu ProSAT]</span></td></tr> | ||
</table> | </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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6qdu" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Andrei SA]] | [[Category: Andrei SA]] | ||
Current revision
Crystal structure of 14-3-3sigma in complex with a RapGef2 pT740 phosphopeptide inhibited by semi-synthetic fusicoccane FC-NCPC
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