5xjd - Revision history

OCA at 08:04, 22 November 2023

OCA — Wed, 22 Nov 2023 08:04:09 GMT

←Older revision		Revision as of 08:04, 22 November 2023
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	<StructureSection load='5xjd' size='340' side='right'caption='[[5xjd]], [[Resolution\|resolution]] 2.22Å' scene=''>		<StructureSection load='5xjd' size='340' side='right'caption='[[5xjd]], [[Resolution\|resolution]] 2.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xjd]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. 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 [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XJD FirstGlance]. <br>	+	<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='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=87L:(2S)~~-2~~-phenyl-2-pyrrol-1-yl-ethanoic+acid'>87L</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]] 2.22Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~Tead4, Tcf13r1, Tef3, Tefr1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=~~5&id=10090 LK3 transgenic mice]~~)</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5xjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjd OCA], [~~http~~://pdbe.org/5xjd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5xjd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5xjd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjd 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=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>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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.	+	[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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Kaan~~, H Y.K~~]]	+	[[Category: Kaan HYK]]
-	[[Category: Sim~~, A Y.L~~]]	+	[[Category: Sim AYL]]
-	[[Category: Song, H]]	+	[[Category: Song H]]
-	[[Category: Tan~~, S K.J~~]]	+	[[Category: Tan SKJ]]
-	[[Category: Verma, C]]	+	[[Category: Verma C]]
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription factor~~]]	+

OCA at 09:02, 1 May 2019

OCA — Wed, 01 May 2019 09:02:16 GMT

←Older revision		Revision as of 09:02, 1 May 2019
Line 1:		Line 1:

	==TEAD in complex with fragment==		==TEAD in complex with fragment==
-	<StructureSection load='5xjd' size='340' side='right' caption='[[5xjd]], [[Resolution\|resolution]] 2.22Å' scene=''>	+	<StructureSection load='5xjd' size='340' side='right'caption='[[5xjd]], [[Resolution\|resolution]] 2.22Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xjd]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XJD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xjd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XJD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=87L:(2S)-2-phenyl-2-pyrrol-1-yl-ethanoic+acid'>87L</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=87L:(2S)-2-phenyl-2-pyrrol-1-yl-ethanoic+acid'>87L</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tead4, Tcf13r1, Tef3, Tefr1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5xjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjd OCA], [http://pdbe.org/5xjd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xjd RCSB], [http://www.ebi.ac.uk/pdbsum/5xjd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjd 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=5xjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjd OCA], [http://pdbe.org/5xjd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xjd RCSB], [http://www.ebi.ac.uk/pdbsum/5xjd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjd ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	The Hippo pathway ~~is a tumor suppressor pathway that~~ is implicated in the regulation of organ size~~. The pathway~~ has ~~three components:~~ the ~~upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists~~ of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD ~~complexes~~ leads to ~~the~~ transcription of growth-promoting genes. ~~Herein~~, ~~we report~~ the ~~crystal structure~~ of ~~TAZ-TEAD4~~ complex, ~~which reveals two binding modes. The first is similar to the published YAP~~-~~TEAD structure. The second is~~ a ~~unique binding mode, whereby two molecules of TAZ bind to and bridge two molecules of TEAD4~~. We ~~validated~~ the ~~latter using cross~~-~~linking and multi~~-~~angle light scattering. Using siRNA~~, we showed that ~~TAZ knockdown leads to~~ a ~~decrease in TEAD4 dimerization. Lastly, results from luciferase assays, using~~ YAP/TAZ ~~transfected or knockdown cells, give support to~~ the ~~non-redundancy~~ of YAP/TAZ co-~~activators in regulating gene expression in the Hippo pathway~~.	+	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.

-	~~Crystal structure of~~ TAZ-TEAD ~~complex reveals a distinct interaction mode from that of YAP~~-~~TEAD complex~~.,Kaan HYK, ~~Chan SW~~, Tan SKJ, ~~Guo F, Lim CJ, Hong W~~, Song H ~~Sci Rep~~. 2017 ~~May 17~~;7(1):~~2035~~. doi: 10.~~1038~~/~~s41598-017-02219-9~~. PMID:~~28515457~~<ref>PMID:~~28515457~~</ref>	+	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®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Kaan, H Y.K]]		[[Category: Kaan, H Y.K]]
	[[Category: Sim, A Y.L]]		[[Category: Sim, A Y.L]]

OCA at 18:25, 24 January 2018

OCA — Wed, 24 Jan 2018 18:25:57 GMT

←Older revision		Revision as of 18:25, 24 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5xjd is ~~ON HOLD~~	+	==TEAD in complex with fragment==
		+	<StructureSection load='5xjd' size='340' side='right' caption='[[5xjd]], [[Resolution\|resolution]] 2.22Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5xjd]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XJD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xjd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjd OCA], [http://pdbe.org/5xjd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xjd RCSB], [http://www.ebi.ac.uk/pdbsum/5xjd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjd ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the transcription of growth-promoting genes. Herein, we report the crystal structure of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to the published YAP-TEAD structure. The second is a unique binding mode, whereby two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the latter using cross-linking and multi-angle light scattering. Using siRNA, we showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly, results from luciferase assays, using YAP/TAZ transfected or knockdown cells, give support to the non-redundancy of YAP/TAZ co-activators in regulating gene expression in the Hippo pathway.

-	~~Authors~~:	+	Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex.,Kaan HYK, Chan SW, Tan SKJ, Guo F, Lim CJ, Hong W, Song H Sci Rep. 2017 May 17;7(1):2035. doi: 10.1038/s41598-017-02219-9. PMID:28515457<ref>PMID:28515457</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5xjd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Kaan, H Y.K]]
		+	[[Category: Sim, A Y.L]]
		+	[[Category: Song, H]]
		+	[[Category: Tan, S K.J]]
		+	[[Category: Verma, C]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription factor]]

OCA: Protected "5xjd" [edit=sysop:move=sysop]

OCA — Wed, 10 May 2017 12:01:24 GMT

Protected "5xjd" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:01, 10 May 2017

OCA: New page: '''Unreleased structure''' The entry 5xjd is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 10 May 2017 12:01:22 GMT

New page: '''Unreleased structure''' The entry 5xjd is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5xjd is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]