7v9b
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7v9b]] 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=7V9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V9B FirstGlance]. <br> | <table><tr><td colspan='2'>[[7v9b]] 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=7V9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V9B FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=323:2-[3,6-BIS(DIMETHYLAMINO)XANTHEN-9-YL]-5-METHANOYL-BENZOATE'>323</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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]] 1.85Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=323:2-[3,6-BIS(DIMETHYLAMINO)XANTHEN-9-YL]-5-METHANOYL-BENZOATE'>323</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=7v9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v9b OCA], [https://pdbe.org/7v9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v9b RCSB], [https://www.ebi.ac.uk/pdbsum/7v9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v9b ProSAT]</span></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=7v9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v9b OCA], [https://pdbe.org/7v9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v9b RCSB], [https://www.ebi.ac.uk/pdbsum/7v9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v9b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/G9K389_HUMAN G9K389_HUMAN] | |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The transcriptional activity of Forkhead Box O3 (FOXO3a) is inactivated by AKT-mediated phosphorylation on Serine 253 (S253), which enables FOXO3a binding to 14-3-3. Phosphorylated FOXO3a binding to 14-3-3 facilitates the nuclear exclusion of FOXO3a, causing cancer cell proliferation. The FOXO3a/14-3-3 interaction has, therefore, emerged as an important therapeutic target. Here, we report a comprehensive analysis using fluorescence polarization, isothermal titration calorimetry, small-angle X-ray scattering, X-ray crystallography, and molecular dynamics simulations to gain molecular-level insights into the interaction of FOXO3a(pS253) phosphopeptide with 14-3-3epsilon. A high-resolution structure of the fluorophore-labeled FOXO3a(pS253):14-3-3epsilon complex revealed a distinct mode of interaction compared to other 14-3-3 phosphopeptide complexes. FOXO3a(pS253) phosphopeptide showed significant structural difference in the positions of the -3 and -4 Arg residues relative to pSer, compared to that of a similar phosphopeptide, FOXO1(pS256) bound to 14-3-3sigma. Moreover, molecular dynamics studies show that the significant structural changes and molecular interactions noticed in the crystal structure of FOXO3a(pS253):14-3-3epsilon are preserved over the course of the simulation. Thus, this study reveals structural differences between the binding to 14-3-3 isoforms of FOXO1(pS256) versus FOXO3a(pS253), providing a framework for the rational design of isoform-specific FOXO/14-3-3 protein-protein interaction inhibitors for therapy. | ||
| + | |||
| + | Structure of a 14-3-3epsilon:FOXO3a(pS253) Phosphopeptide Complex Reveals 14-3-3 Isoform-Specific Binding of Forkhead Box Class O Transcription Factor (FOXO) Phosphoproteins.,Mathivanan S, Chunchagatta Lakshman PK, Singh M, Giridharan S, Sathish K, Hurakadli MA, Bharatham K, Kamariah N ACS Omega. 2022 Jul 5;7(28):24344-24352. doi: 10.1021/acsomega.2c01700., eCollection 2022 Jul 19. PMID:35874228<ref>PMID:35874228</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7v9b" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal Structure of 14-3-3 epsilon with FOXO3a peptide
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