7oyj
From Proteopedia
(Difference between revisions)
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==Crystal structure of hTEAD2 in complex with fragment at the interface 2== | ==Crystal structure of hTEAD2 in complex with fragment at the interface 2== | ||
| - | <StructureSection load='7oyj' size='340' side='right'caption='[[7oyj]]' scene=''> | + | <StructureSection load='7oyj' size='340' side='right'caption='[[7oyj]], [[Resolution|resolution]] 1.91Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OYJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7oyj]] 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=7OYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OYJ FirstGlance]. <br> |
| - | </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=7oyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oyj OCA], [https://pdbe.org/7oyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oyj RCSB], [https://www.ebi.ac.uk/pdbsum/7oyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oyj ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.91Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DI:3-(1~{H}-pyrazol-5-yl)aniline'>3DI</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=7oyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oyj OCA], [https://pdbe.org/7oyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oyj RCSB], [https://www.ebi.ac.uk/pdbsum/7oyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oyj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TEAD2_HUMAN TEAD2_HUMAN] 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 to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3'). May be involved in the gene regulation of neural development. Binds to the M-CAT motif.<ref>PMID:18579750</ref> <ref>PMID:19324877</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Hippo signaling pathway plays a fundamental role in the control of organ growth, cell proliferation, and stem cell characters. TEADs are the main transcriptional output regulators of the Hippo signaling pathway and bind to YAP and TAZ co-activators. TEAD1-4 are expressed differently, depending on the tissue and developmental level, and can be overexpressed in certain pathologies. TEAD ligands mainly target the internal pocket of the C-terminal domain of TEAD, and the first ligands selective for TEAD1 and TEAD3 have been recently reported. In this paper, we focus on the topographic homology of the TEAD C-terminal domain both externally and in the internal pocket to highlight the possibility of rationally designing ligands selective for one of the TEAD family members. We identified a novel TEAD2-specific pocket and reported its first ligand. Finally, AlphaFold2 models of full-length TEADs suggest TEAD autoregulation and emphasize the importance of the interface 2. | ||
| + | |||
| + | Toward the Design of Ligands Selective for the C-Terminal Domain of TEADs.,Liberelle M, Toulotte F, Renault N, Gelin M, Allemand F, Melnyk P, Guichou JF, Cotelle P J Med Chem. 2022 Apr 28;65(8):5926-5940. doi: 10.1021/acs.jmedchem.2c00075. Epub , 2022 Apr 7. PMID:35389210<ref>PMID:35389210</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7oyj" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Allemand F]] | [[Category: Allemand F]] | ||
[[Category: Gelin M]] | [[Category: Gelin M]] | ||
[[Category: Guichou JF]] | [[Category: Guichou JF]] | ||
Current revision
Crystal structure of hTEAD2 in complex with fragment at the interface 2
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