6e5g: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6e5g is ON HOLD  until Paper Publication
+==Crystal structure of human TEAD2-Yap binding domain covalently bound to an allosteric regulator==
+<StructureSection load='6e5g' size='340' side='right'caption='[[6e5g]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6e5g]] 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=6E5G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E5G 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]] 2.43&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HUY:1-(2-{[3-(trifluoromethyl)phenyl]amino}phenyl)ethan-1-one'>HUY</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=6e5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5g OCA], [https://pdbe.org/6e5g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e5g RCSB], [https://www.ebi.ac.uk/pdbsum/6e5g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5g ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The Hippo pathway coordinates extracellular signals onto the control of tissue homeostasis and organ size. Hippo signaling primarily regulates the ability of Yap1 to bind and co-activate TEA domain (TEAD) transcription factors. Yap1 tightly binds to TEAD4 via a large flat interface, making the development of small-molecule orthosteric inhibitors highly challenging. Here, we report small-molecule TEADYap inhibitors that rapidly and selectively form a covalent bond with a conserved cysteine located within the unique deep hydrophobic palmitate-binding pocket of TEADs. Inhibition of TEAD4 binding to Yap1 by these compounds was irreversible and occurred on a longer time scale. In mammalian cells, the compounds formed a covalent complex with TEAD4, inhibited its binding to Yap1, blocked its transcriptional activity, and suppressed expression of connective tissue growth factor. The compounds inhibited cell viability of patient-derived glioblastoma spheroids, making them suitable as chemical probes to explore Hippo signaling in cancer.
-Authors: Bum-Erdene, K., Gonzalez-Gutierrez, G., Meroueh, S.O.
+Small-Molecule Covalent Modification of Conserved Cysteine Leads to Allosteric Inhibition of the TEADYap Protein-Protein Interaction.,Bum-Erdene K, Zhou D, Gonzalez-Gutierrez G, Ghozayel MK, Si Y, Xu D, Shannon HE, Bailey BJ, Corson TW, Pollok KE, Wells CD, Meroueh SO Cell Chem Biol. 2018 Dec 18. pii: S2451-9456(18)30432-X. doi:, 10.1016/j.chembiol.2018.11.010. PMID:30581134<ref>PMID:30581134</ref>
-Description: Crystal structure of human TEAD2-Yap binding domain covalently bound to an allosteric regulator
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Meroueh, S.O]]
+<div class="pdbe-citations 6e5g" style="background-color:#fffaf0;"></div>
-[[Category: Bum-Erdene, K]]
+== References ==
-[[Category: Gonzalez-Gutierrez, G]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bum-Erdene K]]
+[[Category: Gonzalez-Gutierrez G]]
+[[Category: Meroueh SO]]