View source for 6rwu


==Fragment AZ-010 binding at the p53pT387/14-3-3 sigma interface==
<StructureSection load='6rwu' size='340' side='right'caption='[[6rwu]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RWU 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]] 1.46&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KM8:~{N}-[3-(5-carbamimidoylthiophen-3-yl)phenyl]propanamide'>KM8</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=6rwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rwu OCA], [https://pdbe.org/6rwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rwu RCSB], [https://www.ebi.ac.uk/pdbsum/6rwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rwu ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragment-based approach can be used to identify chemical starting points for the development of small-molecule stabilizers that differentiate between two different PPI interfaces of the adapter protein 14-3-3. The fragments discriminately bind to the interface of 14-3-3 with the recognition motif of either the tumor suppressor protein p53 or the oncogenic transcription factor TAZ. This x-ray crystallography driven study shows that the rim of the interface of individual 14-3-3 complexes can be targeted in a differential manner with fragments that represent promising starting points for the development of specific 14-3-3 PPI stabilizers.

Fragment-based Differential Targeting of PPI Stabilizer Interfaces.,Guillory X, Wolter M, Leysen S, Neves JF, Kuusk A, Genet S, Somsen B, Morrow J, Rivers E, van Beek L, Patel J, Goodnow R, Schoenherr H, Fuller N, Cao Q, Doveston RG, Brunsveld L, Arkin MR, Castaldi MP, Boyd H, Landrieu I, Chen H, Ottmann C J Med Chem. 2020 Jun 5. doi: 10.1021/acs.jmedchem.9b01942. PMID:32501690<ref>PMID:32501690</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rwu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Castaldi P]]
[[Category: Genet S]]
[[Category: Guillory X]]
[[Category: Leysen S]]
[[Category: Ottmann C]]
[[Category: Patel J]]
[[Category: Somsen B]]
[[Category: Wolter M]]