View source for 6ypy


==14-3-3 sigma with RelA/p65 binding site pS45 and covalently bound TCF521-123==
<StructureSection load='6ypy' size='340' side='right'caption='[[6ypy]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ypy]] 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=6YPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YPY 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=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=P7E:4-(4-ethanoylpiperazin-1-yl)sulfonylbenzaldehyde'>P7E</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=6ypy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ypy OCA], [https://pdbe.org/6ypy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ypy RCSB], [https://www.ebi.ac.uk/pdbsum/6ypy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ypy ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Small-molecule stabilization of protein-protein interactions (PPI) is a promising concept in drug discovery, however the question how to identify or design chemical starting points in a 'bottom-up' approach is largely unanswered. Here we report a novel concept for identifying initial chemical matter for PPI stabilization based on covalent imine forming fragments. The imine bond offers a covalent anchor for site-directed fragment targeting, whereas its transient nature allows an efficient structure activity relationship analysis. This bond enables fragment identification and optimisation using protein crystallography. We report novel fragments which bind specifically to a lysine at the PPI interface of the p65 subunit-derived peptide of NF-kappaB with the adapter protein 14-3-3. Those fragments that subsequently establish contacts with the p65-derived peptide, rather than with 14-3-3, efficiently stabilize the 14-3-3/p65 complex and offer novel starting points for molecular glues.

Fragment Based Protein-Protein Interaction Stabilizers via Imine-Based Tethering.,Ottmann C, Wolter M, Valenti D, Cossar PJ, Levy LM, Hristeva S, Genski T, Hoffmann T, Brunsveld L, Tzalis D Angew Chem Int Ed Engl. 2020 Aug 20. doi: 10.1002/anie.202008585. PMID:32816380<ref>PMID:32816380</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ypy" 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: Ottmann C]]
[[Category: Wolter M]]