View source for 7bmc


==Crystal structure of 14-3-3 sigma in complex with CIP2ApS904 peptide and stabilizing Fusicoccin A==
<StructureSection load='7bmc' size='340' side='right'caption='[[7bmc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7bmc]] 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=7BMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BMC 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]] 2&#8491;</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=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=FSC:FUSICOCCIN'>FSC</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'>[https://proteopedia.org/fgij/fg.htm?mol=7bmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bmc OCA], [https://pdbe.org/7bmc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bmc RCSB], [https://www.ebi.ac.uk/pdbsum/7bmc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bmc 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 cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein found overexpressed in many types of cancer. CIP2A has been shown to stabilize oncoproteins such as cMYC by shielding them from PP2A-mediated dephosphorylation. Here we report that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated to create a binding site for the regulatory protein 14-3-3. We demonstrate that 14-3-3 is a new interaction partner of CIP2A. The 14-3-3/CIP2A C-terminal interaction complex can be targeted by the protein-protein interaction (PPI) stabilizer fusicoccin-A (FC-A), resulting in enhanced levels of phosphorylated Ser904. FC-A treatment of TNBC cells leads to the increased association of CIP2A with 14-3-3. We show that the composite interface between 14 and 3-3 and CIP2A's C-terminus can be targeted by the PPI stabilizer FC-A, providing a new interface that could potentially be exploited to modulate CIP2A's activity.

Fusicoccin-A Targets Cancerous Inhibitor of Protein Phosphatase 2A by Stabilizing a C-Terminal Interaction with 14-3-3.,Brink HJ, van Senten JR, De Vries-van Leeuwen IJ, da Costa Pereira D, Piersma SR, Jimenez CR, Centorrino F, Ottmann C, Siderius M, Smit MJ, de Boer AH ACS Chem Biol. 2022 Nov 18;17(11):2972-2978. doi: 10.1021/acschembio.2c00299. , Epub 2022 Oct 18. PMID:36255265<ref>PMID:36255265</ref>

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

==See Also==
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Andlovic B]]
[[Category: Centorrino F]]
[[Category: Ottmann C]]