5yj8 - Revision history

OCA at 08:31, 22 November 2023

OCA — Wed, 22 Nov 2023 08:31:51 GMT

←Older revision		Revision as of 08:31, 22 November 2023
Line 1:		Line 1:

	==Identification of a small molecule inhibitor for the Tudor domain of TDRD3==		==Identification of a small molecule inhibitor for the Tudor domain of TDRD3==
-	<StructureSection load='5yj8' size='340' side='right' caption='[[5yj8]], [[Resolution\|resolution]] 1.76Å' scene=''>	+	<StructureSection load='5yj8' size='340' side='right'caption='[[5yj8]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5yj8]] is a 1 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=5YJ8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5YJ8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5yj8]] is a 1 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=5YJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YJ8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8W9:5-(aminomethyl)-1,3-dimethyl-benzimidazol-2-one'>8W9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.762Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TDRD3 ([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=8W9:5-(aminomethyl)-1,3-dimethyl-benzimidazol-2-one'>8W9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5yj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj8 OCA], [~~http~~://pdbe.org/5yj8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5yj8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5yj8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj8 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=5yj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj8 OCA], [https://pdbe.org/5yj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yj8 RCSB], [https://www.ebi.ac.uk/pdbsum/5yj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TDRD3_HUMAN TDRD3_HUMAN]] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.<ref>PMID:18632687</ref> <ref>PMID:15955813</ref> <ref>PMID:21172665</ref>	+	[https://www.uniprot.org/uniprot/TDRD3_HUMAN TDRD3_HUMAN] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.<ref>PMID:18632687</ref> <ref>PMID:15955813</ref> <ref>PMID:21172665</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: ~~Liu, J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Ruan, K~~]]	+	[[Category: Liu J]]
-	[[Category: ~~Complex]]~~	+	[[Category: Ruan K]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transcription-inhibitor complex]]~~	+
-	~~[[Category: Transcriptional coactivator~~]]	+

OCA at 05:54, 16 May 2018

OCA — Wed, 16 May 2018 05:54:48 GMT

←Older revision		Revision as of 05:54, 16 May 2018
Line 3:		Line 3:
	<StructureSection load='5yj8' size='340' side='right' caption='[[5yj8]], [[Resolution\|resolution]] 1.76Å' scene=''>		<StructureSection load='5yj8' size='340' side='right' caption='[[5yj8]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5yj8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YJ8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5yj8]] is a 1 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=5YJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YJ8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8W9:5-(aminomethyl)-1,3-dimethyl-benzimidazol-2-one'>8W9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8W9:5-(aminomethyl)-1,3-dimethyl-benzimidazol-2-one'>8W9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TDRD3 ([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=5yj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj8 OCA], [http://pdbe.org/5yj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yj8 RCSB], [http://www.ebi.ac.uk/pdbsum/5yj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj8 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=5yj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj8 OCA], [http://pdbe.org/5yj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yj8 RCSB], [http://www.ebi.ac.uk/pdbsum/5yj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/TDRD3_HUMAN TDRD3_HUMAN]] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.<ref>PMID:18632687</ref> <ref>PMID:15955813</ref> <ref>PMID:21172665</ref>		[[http://www.uniprot.org/uniprot/TDRD3_HUMAN TDRD3_HUMAN]] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.<ref>PMID:18632687</ref> <ref>PMID:15955813</ref> <ref>PMID:21172665</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	As a reader of di-methylated arginine on various proteins, such as histone, RNA polymerase II, PIWI and Fragile X mental retardation protein, the Tudor domain of Tudor domain-containing protein 3 (TDRD3) mediates transcriptional activation in nucleus and formation of stress granules in the cytoplasm. Despite the TDRD3 implication in cancer cell proliferation and invasion, warheads to block the di-methylated arginine recognition pocket of the TDRD3 Tudor domain have not yet been uncovered. Here we identified 14 small molecule hits against the TDRD3 Tudor domain through NMR fragment-based screening. These hits were further cross-validated by using competitive fluorescence polarization and isothermal titration calorimetry experiments. The crystal structure of the TDRD3 Tudor domain in complex with hit 1 reveals a distinct binding mode from the nature substrate. Hit 1 protrudes into the aromatic cage of the TDRD3 Tudor domain, where the aromatic residues are tilted to accommodate a sandwich-like pi-pi interaction. The side chain of the conserved residue N596 swings away 3.1 A to form a direct hydrogen bond with hit 1. Moreover, this compound shows a decreased affinity against the single Tudor domain of survival motor neuron protein, but no detectable binding to neither the tandem Tudor domain of TP53-binding protein 1 nor the extended Tudor domain of staphylococcal nuclease domain-containing protein 1. Our work depicts the structural plasticity of the TDRD3 Tudor domain and paves the way for the subsequent structure-guided discovery of selective inhibitors targeting Tudor domains. DATABASE: Structural data are available in the PDB under the accession number 5YJ8.
		+
		+	Structural plasticity of the TDRD3 Tudor domain probed by a fragment screening hit.,Liu J, Zhang S, Liu M, Liu Y, Nshogoza G, Gao J, Ma R, Yang Y, Wu J, Zhang J, Li F, Ruan K FEBS J. 2018 Apr 12. doi: 10.1111/febs.14469. PMID:29645362<ref>PMID:29645362</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5yj8" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Liu, J]]		[[Category: Liu, J]]
	[[Category: Ruan, K]]		[[Category: Ruan, K]]

OCA at 08:05, 2 May 2018

OCA — Wed, 02 May 2018 08:05:35 GMT

←Older revision		Revision as of 08:05, 2 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5yj8 is ON HOLD until Paper Publication~~	+	==Identification of a small molecule inhibitor for the Tudor domain of TDRD3==
-		+	<StructureSection load='5yj8' size='340' side='right' caption='[[5yj8]], [[Resolution\|resolution]] 1.76Å' scene=''>
-	~~Authors: Liu, J., Ruan, K.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5yj8]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YJ8 FirstGlance]. <br>
-	~~Description:~~ Identification of a small molecule inhibitor for the Tudor domain of TDRD3	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8W9:5-(aminomethyl)-1,3-dimethyl-benzimidazol-2-one'>8W9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=5yj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yj8 OCA], [http://pdbe.org/5yj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yj8 RCSB], [http://www.ebi.ac.uk/pdbsum/5yj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yj8 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TDRD3_HUMAN TDRD3_HUMAN]] Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins.<ref>PMID:18632687</ref> <ref>PMID:15955813</ref> <ref>PMID:21172665</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Liu, J]]		[[Category: Liu, J]]
	[[Category: Ruan, K]]		[[Category: Ruan, K]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transcription-inhibitor complex]]
		+	[[Category: Transcriptional coactivator]]

OCA at 17:09, 24 January 2018

OCA — Wed, 24 Jan 2018 17:09:13 GMT

←Older revision		Revision as of 17:09, 24 January 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5yj8 is ON HOLD	+	The entry 5yj8 is ON HOLD until Paper Publication

	Authors: Liu, J., Ruan, K.		Authors: Liu, J., Ruan, K.

OCA at 05:29, 17 January 2018

OCA — Wed, 17 Jan 2018 05:29:49 GMT

←Older revision		Revision as of 05:29, 17 January 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5yj8 is ON HOLD ~~until Paper Publication~~	+	The entry 5yj8 is ON HOLD

	Authors: Liu, J., Ruan, K.		Authors: Liu, J., Ruan, K.

OCA: Protected "5yj8" [edit=sysop:move=sysop]

OCA — Wed, 25 Oct 2017 05:36:30 GMT

Protected "5yj8" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:36, 25 October 2017

OCA: New page: '''Unreleased structure''' The entry 5yj8 is ON HOLD until Paper Publication Authors: Liu, J., Ruan, K. Description: Identification of a small molecule inhibitor for the Tudor domain o...

OCA — Wed, 25 Oct 2017 05:36:28 GMT

New page: '''Unreleased structure''' The entry 5yj8 is ON HOLD until Paper Publication Authors: Liu, J., Ruan, K. Description: Identification of a small molecule inhibitor for the Tudor domain o...

New page

'''Unreleased structure'''

The entry 5yj8 is ON HOLD until Paper Publication

Authors: Liu, J., Ruan, K.

Description: Identification of a small molecule inhibitor for the Tudor domain of TDRD3
[[Category: Unreleased Structures]]
[[Category: Liu, J]]
[[Category: Ruan, K]]