6e5g - Revision history

OCA at 06:19, 11 October 2023

2023-10-11T06:19:18Z

←Older revision		Revision as of 06:19, 11 October 2023
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	<StructureSection load='6e5g' size='340' side='right'caption='[[6e5g]], [[Resolution\|resolution]] 2.43Å' scene=''>		<StructureSection load='6e5g' size='340' side='right'caption='[[6e5g]], [[Resolution\|resolution]] 2.43Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e5g]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. 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 [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6E5G FirstGlance]. <br>	+	<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='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=HUY:1~~-~~(2-{~~[~~3-(trifluoromethyl)phenyl~~]~~amino}phenyl)ethan-1-one'>HUY</scene>~~</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]] 2.43Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~TEAD2, TEF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=~~5&id=9606 HUMAN~~])</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6e5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5g OCA], [~~http~~://pdbe.org/6e5g PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6e5g RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6e5g PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5g ProSAT]</span></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>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bum-Erdene, K]]	+	[[Category: Bum-Erdene K]]
-	[[Category: Gonzalez-Gutierrez, G]]	+	[[Category: Gonzalez-Gutierrez G]]
-	[[Category: Meroueh~~, S O]]~~	+	[[Category: Meroueh SO]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transcription-inhibitor complex~~]]	+

OCA at 08:12, 3 April 2019

2019-04-03T08:12:09Z

←Older revision		Revision as of 08:12, 3 April 2019
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	==Crystal structure of human TEAD2-Yap binding domain covalently bound to an allosteric regulator==		==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]] 2.43Å' scene=''>	+	<StructureSection load='6e5g' size='340' side='right'caption='[[6e5g]], [[Resolution\|resolution]] 2.43Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6e5g]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E5G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6e5g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E5G FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HUY:1-(2-{[3-(trifluoromethyl)phenyl]amino}phenyl)ethan-1-one'>HUY</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HUY:1-(2-{[3-(trifluoromethyl)phenyl]amino}phenyl)ethan-1-one'>HUY</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TEAD2, TEF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5g OCA], [http://pdbe.org/6e5g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e5g RCSB], [http://www.ebi.ac.uk/pdbsum/6e5g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5g ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5g OCA], [http://pdbe.org/6e5g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e5g RCSB], [http://www.ebi.ac.uk/pdbsum/6e5g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5g ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bum-Erdene, K]]		[[Category: Bum-Erdene, K]]
	[[Category: Gonzalez-Gutierrez, G]]		[[Category: Gonzalez-Gutierrez, G]]

OCA at 06:35, 9 January 2019

2019-01-09T06:35:32Z

←Older revision		Revision as of 06:35, 9 January 2019
Line 1:		Line 1:
-	'''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]] 2.43Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6e5g]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E5G FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5g OCA], [http://pdbe.org/6e5g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e5g RCSB], [http://www.ebi.ac.uk/pdbsum/6e5g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5g ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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 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®/PubMed®, 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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Bum-Erdene, K]]		[[Category: Bum-Erdene, K]]
	[[Category: Gonzalez-Gutierrez, G]]		[[Category: Gonzalez-Gutierrez, G]]
		+	[[Category: Meroueh, S O]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transcription-inhibitor complex]]

OCA: Protected "6e5g" [edit=sysop:move=sysop]

2018-08-01T17:03:39Z

Protected "6e5g" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:03, 1 August 2018

OCA: New page: '''Unreleased structure''' The entry 6e5g is ON HOLD until Paper Publication Authors: Bum-Erdene, K., Gonzalez-Gutierrez, G., Meroueh, S.O. Description: Crystal structure of human TEAD...

2018-08-01T17:03:37Z

New page: '''Unreleased structure''' The entry 6e5g is ON HOLD until Paper Publication Authors: Bum-Erdene, K., Gonzalez-Gutierrez, G., Meroueh, S.O. Description: Crystal structure of human TEAD...

New page

'''Unreleased structure'''

The entry 6e5g is ON HOLD until Paper Publication

Authors: Bum-Erdene, K., Gonzalez-Gutierrez, G., Meroueh, S.O.

Description: Crystal structure of human TEAD2-Yap binding domain covalently bound to an allosteric regulator
[[Category: Unreleased Structures]]
[[Category: Meroueh, S.O]]
[[Category: Bum-Erdene, K]]
[[Category: Gonzalez-Gutierrez, G]]