View source for 6slw


==Fragment AZ-004 binding at the TAZpS89/14-3-3 sigma interface==
<StructureSection load='6slw' size='340' side='right'caption='[[6slw]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SLW 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=L1T:4-methyl-5-phenyl-thiophene-2-carboximidamide'>L1T</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=6slw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6slw OCA], [https://pdbe.org/6slw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6slw RCSB], [https://www.ebi.ac.uk/pdbsum/6slw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6slw ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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 6slw" 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]]