View source for 5xjd


==TEAD in complex with fragment==
<StructureSection load='5xjd' size='340' side='right'caption='[[5xjd]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5xjd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XJD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XJD 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]] 2.22&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=87L:(2S)-2-phenyl-2-pyrrol-1-yl-ethanoic+acid'>87L</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=5xjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjd OCA], [https://pdbe.org/5xjd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xjd RCSB], [https://www.ebi.ac.uk/pdbsum/5xjd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TEAD4_MOUSE TEAD4_MOUSE] Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif (By similarity). Might play a role in the embryonic development of skeletal muscle.
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== Publication Abstract from PubMed ==
The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment. We confirmed its binding at the YAP/TAZ-TEAD interface by X-ray crystallography, and showed that it occupies the same hydrophobic pocket as a conserved phenylalanine of YAP/TAZ. This hit fragment serves as a scaffold for the development of compounds that have the potential to disrupt YAP/TAZ-TEAD interactions. Structure-activity relationship studies and computational modeling were also carried out to identify more potent compounds that may bind at this validated druggable binding site.

Targeting YAP/TAZ-TEAD protein-protein interactions using fragment-based and computational modeling approaches.,Kaan HYK, Sim AYL, Tan SKJ, Verma C, Song H PLoS One. 2017 Jun 1;12(6):e0178381. doi: 10.1371/journal.pone.0178381., eCollection 2017. PMID:28570566<ref>PMID:28570566</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5xjd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Kaan HYK]]
[[Category: Sim AYL]]
[[Category: Song H]]
[[Category: Tan SKJ]]
[[Category: Verma C]]