4ybt - Revision history

OCA at 07:56, 27 September 2023

OCA — Wed, 27 Sep 2023 07:56:25 GMT

←Older revision		Revision as of 07:56, 27 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ybt]] 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=4YBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YBT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ybt]] 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=4YBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YBT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.82Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [https://pdbe.org/4ybt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [https://www.ebi.ac.uk/pdbsum/4ybt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ybt 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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [https://pdbe.org/4ybt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [https://www.ebi.ac.uk/pdbsum/4ybt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ybt ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:07, 3 May 2023

OCA — Wed, 03 May 2023 08:07:49 GMT

←Older revision		Revision as of 08:07, 3 May 2023
Line 3:		Line 3:
	<StructureSection load='4ybt' size='340' side='right'caption='[[4ybt]], [[Resolution\|resolution]] 1.82Å' scene=''>		<StructureSection load='4ybt' size='340' side='right'caption='[[4ybt]], [[Resolution\|resolution]] 1.82Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ybt]] 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=4YBT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4YBT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ybt]] 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=4YBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YBT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yab\|4yab]], [[4yad\|4yad]], [[4yat\|4yat]], [[4yax\|4yax]], [[4ybm\|4ybm]], [[4ybs\|4ybs]], [[4yc9\|4yc9]]</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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [https://pdbe.org/4ybt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [https://www.ebi.ac.uk/pdbsum/4ybt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ybt ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TRIM24, RNF82, TIF1, TIF1A ([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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [~~http~~://pdbe.org/4ybt PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ybt PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ybt ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN]] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:[~~http~~://omim.org/entry/188550 188550]]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.	+	[https://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN]] Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).<ref>PMID:16322096</ref> <ref>PMID:19556538</ref> <ref>PMID:21164480</ref>	+	[https://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN] Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).<ref>PMID:16322096</ref> <ref>PMID:19556538</ref> <ref>PMID:21164480</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Jones, P]]	+	[[Category: Jones P]]
-	[[Category: Palmer, W]]	+	[[Category: Palmer W]]
-	[[Category: Poncet-Montange, G]]	+	[[Category: Poncet-Montange G]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Center for biomolecular structure and function]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Transcription-transcription inhibitor complex]]~~	+
-	~~[[Category: Trim24~~]]	+

OCA at 06:55, 12 June 2019

OCA — Wed, 12 Jun 2019 06:55:35 GMT

←Older revision		Revision as of 06:55, 12 June 2019
Line 1:		Line 1:

	==Crystal structure of TRIM24 PHD-bromodomain complexed with N-{1,3-dimethyl-2-oxo-6-[3-(oxolan-3-ylmethoxy)phenoxy]-2,3-dihydro-1H-1,3-benzodiazol-5-yl}-1-methyl-1H-imidazole-4-sulfonamide (7l)==		==Crystal structure of TRIM24 PHD-bromodomain complexed with N-{1,3-dimethyl-2-oxo-6-[3-(oxolan-3-ylmethoxy)phenoxy]-2,3-dihydro-1H-1,3-benzodiazol-5-yl}-1-methyl-1H-imidazole-4-sulfonamide (7l)==
-	<StructureSection load='4ybt' size='340' side='right' caption='[[4ybt]], [[Resolution\|resolution]] 1.82Å' scene=''>	+	<StructureSection load='4ybt' size='340' side='right'caption='[[4ybt]], [[Resolution\|resolution]] 1.82Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ybt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YBT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ybt]] 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=4YBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YBT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yab\|4yab]], [[4yad\|4yad]], [[4yat\|4yat]], [[4yax\|4yax]], [[4ybm\|4ybm]], [[4ybs\|4ybs]], [[4yc9\|4yc9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yab\|4yab]], [[4yad\|4yad]], [[4yat\|4yat]], [[4yax\|4yax]], [[4ybm\|4ybm]], [[4ybs\|4ybs]], [[4yc9\|4yc9]]</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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [http://pdbe.org/4ybt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [http://www.ebi.ac.uk/pdbsum/4ybt PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TRIM24, RNF82, TIF1, TIF1A ([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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [http://pdbe.org/4ybt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [http://www.ebi.ac.uk/pdbsum/4ybt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ybt ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Jones, P]]		[[Category: Jones, P]]
	[[Category: Palmer, W]]		[[Category: Palmer, W]]

OCA at 20:06, 9 March 2016

OCA — Wed, 09 Mar 2016 20:06:07 GMT

←Older revision		Revision as of 20:06, 9 March 2016
Line 1:		Line 1:
		+
	==Crystal structure of TRIM24 PHD-bromodomain complexed with N-{1,3-dimethyl-2-oxo-6-[3-(oxolan-3-ylmethoxy)phenoxy]-2,3-dihydro-1H-1,3-benzodiazol-5-yl}-1-methyl-1H-imidazole-4-sulfonamide (7l)==		==Crystal structure of TRIM24 PHD-bromodomain complexed with N-{1,3-dimethyl-2-oxo-6-[3-(oxolan-3-ylmethoxy)phenoxy]-2,3-dihydro-1H-1,3-benzodiazol-5-yl}-1-methyl-1H-imidazole-4-sulfonamide (7l)==
	<StructureSection load='4ybt' size='340' side='right' caption='[[4ybt]], [[Resolution\|resolution]] 1.82Å' scene=''>		<StructureSection load='4ybt' size='340' side='right' caption='[[4ybt]], [[Resolution\|resolution]] 1.82Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yab\|4yab]], [[4yad\|4yad]], [[4yat\|4yat]], [[4yax\|4yax]], [[4ybm\|4ybm]], [[4ybs\|4ybs]], [[4yc9\|4yc9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yab\|4yab]], [[4yad\|4yad]], [[4yat\|4yat]], [[4yax\|4yax]], [[4ybm\|4ybm]], [[4ybs\|4ybs]], [[4yc9\|4yc9]]</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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [http://www.ebi.ac.uk/pdbsum/4ybt PDBsum]</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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [http://pdbe.org/4ybt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [http://www.ebi.ac.uk/pdbsum/4ybt PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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>
	</div>		</div>
		+	<div class="pdbe-citations 4ybt" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:57, 24 June 2015

OCA — Wed, 24 Jun 2015 12:57:20 GMT

←Older revision		Revision as of 12:57, 24 June 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of TRIM24 PHD-bromodomain complexed with N-{1,3-dimethyl-2-oxo-6-[3-(oxolan-3-ylmethoxy)phenoxy]-2,3-dihydro-1H-1,3-benzodiazol-5-yl}-1-methyl-1H-imidazole-4-sulfonamide (7l)==
		+	<StructureSection load='4ybt' size='340' side='right' caption='[[4ybt]], [[Resolution\|resolution]] 1.82Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ybt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YBT FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4BV:N-(1,3-DIMETHYL-2-OXO-6-{3-[(3S)-TETRAHYDROFURAN-3-YLMETHOXY]PHENOXY}-2,3-DIHYDRO-1H-BENZIMIDAZOL-5-YL)-1-METHYL-1H-IMIDAZOLE-4-SULFONAMIDE'>4BV</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4yab\|4yab]], [[4yad\|4yad]], [[4yat\|4yat]], [[4yax\|4yax]], [[4ybm\|4ybm]], [[4ybs\|4ybs]], [[4yc9\|4yc9]]</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=4ybt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ybt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ybt RCSB], [http://www.ebi.ac.uk/pdbsum/4ybt PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN]] Defects in TRIM24 are a cause of thyroid papillary carcinoma (TPC) [MIM:[http://omim.org/entry/188550 188550]]. TPC is a common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=A chromosomal aberration involving TRIM24/TIF1 is found in thyroid papillary carcinomas. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TIF1A_HUMAN TIF1A_HUMAN]] Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity).<ref>PMID:16322096</ref> <ref>PMID:19556538</ref> <ref>PMID:21164480</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The bromodomain containing proteins TRIM24 (Tripartite motif containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are involved in the epigenetic regulation of gene expression and have been implicated in human cancer. Overexpression of TRIM24 correlates with poor patient prognosis and BRPF1 is a scaffolding protein required for the assembly of histone acetyltransferase complexes, where the gene of MOZ (monocytic leukemia zinc finger protein) was first identified as a recurrent fusion partner in leukemia patients (8p11 chromosomal rearrangements). Here, we present the structure guided development of a series of N,N-dimethyl benzimidazolone bromodomain inhibitors through the iterative use of X-ray co-crystal structures. A unique binding mode enabled the design of a potent and selective inhibitor, 8i (IACS-9571) with low nanomolar affinities for TRIM24 and BRPF1 (ITC Kd = 31 nM and 14 nM, respectively). With its excellent cellular potency (EC50 = 50 nM) and favorable pharmacokinetic properties (F = 29%), 8i is a high-quality chemical probe for the evaluation of TRIM24 and/or BRPF1 bromodomain function in vitro and in vivo.

-	~~The entry 4ybt is ON HOLD until Paper Publication~~	+	Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor.,Palmer WS, Poncet-Montange G, Liu G, Petrocchi A, Reyna N, Subramanian G, Theroff J, Yau A, Kost-Alimova M, Bardenhagen JP, Leo E, Shepard HE, Tieu TN, Shi X, Zhan Y, Zhao S, Draetta G, Toniatti C, Jones P, Geck Do M, Andersen JN J Med Chem. 2015 Jun 10. PMID:26061247<ref>PMID:26061247</ref>

-	~~Authors: Poncet-Montange~~, G.~~, Palmer, W~~.~~, Jones, P~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Crystal structure of TRIM24 PHD-bromodomain complexed with (7l)~~	+	== References ==
-	~~[[Category: Unreleased Structures]]~~	+	<references/>
-	~~[[Category: Poncet-Montange, G]]~~	+	__TOC__
		+	</StructureSection>
	[[Category: Jones, P]]		[[Category: Jones, P]]
	[[Category: Palmer, W]]		[[Category: Palmer, W]]
		+	[[Category: Poncet-Montange, G]]
		+	[[Category: Bromodomain]]
		+	[[Category: Center for biomolecular structure and function]]
		+	[[Category: Inhibitor]]
		+	[[Category: Transcription-transcription inhibitor complex]]
		+	[[Category: Trim24]]

OCA at 12:18, 26 March 2015

OCA — Thu, 26 Mar 2015 12:18:41 GMT

←Older revision		Revision as of 12:18, 26 March 2015
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	The entry 4ybt is ON HOLD until Paper Publication		The entry 4ybt is ON HOLD until Paper Publication

-	Authors: Poncet-Montange, G., ~~Alimova~~, ~~M., Andersen, J., Bardenhagen, J., Barton, M., Geck Do, M~~., Jones, P~~., Leo, E., Lee, G., Petrocchi, A., Reyna, N., Shepard, H., Subrumanian, G., Theroff, J., Toniatti, C., Shi, X., Yau, A., Zhan, Y., Palmer, W~~.	+	Authors: Poncet-Montange, G., Palmer, W., Jones, P.

	Description: Crystal structure of TRIM24 PHD-bromodomain complexed with (7l)		Description: Crystal structure of TRIM24 PHD-bromodomain complexed with (7l)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Alimova, M]]
-	[[Category: Subrumanian, G]]
-	[[Category: Zhan, Y]]
-	[[Category: Andersen, J]]
-	[[Category: Geck Do, M]]
	[[Category: Poncet-Montange, G]]		[[Category: Poncet-Montange, G]]
	[[Category: Jones, P]]		[[Category: Jones, P]]
-	[[Category: Toniatti, C]]
-	[[Category: Shi, X]]
-	[[Category: Reyna, N]]
-	[[Category: Leo, E]]
-	[[Category: Shepard, H]]
-	[[Category: Theroff, J]]
-	[[Category: Yau, A]]
-	[[Category: Petrocchi, A]]
-	[[Category: Lee, G]]
-	[[Category: Barton, M]]
-	[[Category: Bardenhagen, J]]
	[[Category: Palmer, W]]		[[Category: Palmer, W]]

OCA at 10:34, 18 March 2015

OCA — Wed, 18 Mar 2015 10:34:39 GMT

←Older revision		Revision as of 10:34, 18 March 2015
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ybt is ON HOLD	+	The entry 4ybt is ON HOLD until Paper Publication

	Authors: Poncet-Montange, G., Alimova, M., Andersen, J., Bardenhagen, J., Barton, M., Geck Do, M., Jones, P., Leo, E., Lee, G., Petrocchi, A., Reyna, N., Shepard, H., Subrumanian, G., Theroff, J., Toniatti, C., Shi, X., Yau, A., Zhan, Y., Palmer, W.		Authors: Poncet-Montange, G., Alimova, M., Andersen, J., Bardenhagen, J., Barton, M., Geck Do, M., Jones, P., Leo, E., Lee, G., Petrocchi, A., Reyna, N., Shepard, H., Subrumanian, G., Theroff, J., Toniatti, C., Shi, X., Yau, A., Zhan, Y., Palmer, W.

OCA: Protected "4ybt" [edit=sysop:move=sysop]

OCA — Wed, 25 Feb 2015 12:57:45 GMT

Protected "4ybt" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:57, 25 February 2015

OCA: New page: '''Unreleased structure''' The entry 4ybt is ON HOLD Authors: Poncet-Montange, G., Alimova, M., Andersen, J., Bardenhagen, J., Barton, M., Geck Do, M., Jones, P., Leo, E., Lee, G., Petr...

OCA — Wed, 25 Feb 2015 12:57:44 GMT

New page: '''Unreleased structure''' The entry 4ybt is ON HOLD Authors: Poncet-Montange, G., Alimova, M., Andersen, J., Bardenhagen, J., Barton, M., Geck Do, M., Jones, P., Leo, E., Lee, G., Petr...

New page

'''Unreleased structure'''

The entry 4ybt is ON HOLD

Authors: Poncet-Montange, G., Alimova, M., Andersen, J., Bardenhagen, J., Barton, M., Geck Do, M., Jones, P., Leo, E., Lee, G., Petrocchi, A., Reyna, N., Shepard, H., Subrumanian, G., Theroff, J., Toniatti, C., Shi, X., Yau, A., Zhan, Y., Palmer, W.

Description: Crystal structure of TRIM24 PHD-bromodomain complexed with (7l)
[[Category: Unreleased Structures]]
[[Category: Alimova, M]]
[[Category: Subrumanian, G]]
[[Category: Zhan, Y]]
[[Category: Andersen, J]]
[[Category: Geck Do, M]]
[[Category: Poncet-Montange, G]]
[[Category: Jones, P]]
[[Category: Toniatti, C]]
[[Category: Shi, X]]
[[Category: Reyna, N]]
[[Category: Leo, E]]
[[Category: Shepard, H]]
[[Category: Theroff, J]]
[[Category: Yau, A]]
[[Category: Petrocchi, A]]
[[Category: Lee, G]]
[[Category: Barton, M]]
[[Category: Bardenhagen, J]]
[[Category: Palmer, W]]