8puy
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 8puy is ON HOLD Authors: Guichou, J.F., Gelin, M., Allemand, F. Description: TEAD2 with a covalent inhibitor Category: Unreleased Structures [[...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==TEAD2 with a covalent inhibitor== | |
| + | <StructureSection load='8puy' size='340' side='right'caption='[[8puy]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8puy]] 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=8PUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PUY 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]] 2.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F3Y:~{N}-[3-[(3-pentoxyphenyl)amino]phenyl]propanamide'>F3Y</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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=8puy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8puy OCA], [https://pdbe.org/8puy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8puy RCSB], [https://www.ebi.ac.uk/pdbsum/8puy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8puy ProSAT]</span></td></tr> | ||
| + | </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 transcription factor YAP-TEAD is the downstream effector of the Hippo pathway which controls cell proliferation, apoptosis, tissue repair, and organ growth. Dysregulation of the Hippo pathway has been correlated with carcinogenic processes. A co-crystal structure of TEAD with its endogenous ligand palmitic acid (PA) as well as with flufenamic acid (FA) has been disclosed. Here we report the development of HC-258, which derives from FA and possesses an oxopentyl chain that mimics a molecule of PA as well as an acrylamide that reacts covalently with TEAD's cysteine. HC-258 reduces the CTGF, CYR61, AXL, and NF2 transcript levels and inhibits the migration of MDA-MB-231 breast cancer cells. Co-crystallization with hTEAD2 confirmed that HC-258 binds within TEAD's PA pocket, where it forms a covalent bond with its cysteine. | ||
| - | + | Development of HC-258, a Covalent Acrylamide TEAD Inhibitor That Reduces Gene Expression and Cell Migration.,Fnaiche A, Chan HC, Paquin A, Gonzalez Suarez N, Vu V, Li F, Allali-Hassani A, Cao MA, Szewczyk MM, Bolotokova A, Allemand F, Gelin M, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Guichou JF, Annabi B, Gagnon A ACS Med Chem Lett. 2023 Nov 30;14(12):1746-1753. doi: , 10.1021/acsmedchemlett.3c00386. eCollection 2023 Dec 14. PMID:38116405<ref>PMID:38116405</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8puy" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Allemand F]] | ||
| + | [[Category: Gelin M]] | ||
| + | [[Category: Guichou JF]] | ||
Current revision
TEAD2 with a covalent inhibitor
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