4oq3 - Revision history

OCA at 17:17, 20 September 2023

OCA — Wed, 20 Sep 2023 17:17:46 GMT

←Older revision		Revision as of 17:17, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4oq3]] is a 4 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=4OQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OQ3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4oq3]] is a 4 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=4OQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OQ3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2V8:1-(5-CHLORO-2-METHYLPHENYL)-5-(3-CHLOROPHENYL)-2-(3-METHYLPHENYL)-1H-IMIDAZOLE-4-CARBOXYLIC+ACID'>2V8</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]] 2.3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2V8:1-(5-CHLORO-2-METHYLPHENYL)-5-(3-CHLOROPHENYL)-2-(3-METHYLPHENYL)-1H-IMIDAZOLE-4-CARBOXYLIC+ACID'>2V8</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=4oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq3 OCA], [https://pdbe.org/4oq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oq3 RCSB], [https://www.ebi.ac.uk/pdbsum/4oq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oq3 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=4oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq3 OCA], [https://pdbe.org/4oq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oq3 RCSB], [https://www.ebi.ac.uk/pdbsum/4oq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oq3 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:39, 25 January 2023

OCA — Wed, 25 Jan 2023 07:39:24 GMT

←Older revision		Revision as of 07:39, 25 January 2023
Line 1:		Line 1:

	==Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction==		==Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction==
-	<StructureSection load='4oq3' size='340' side='right' caption='[[4oq3]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='4oq3' size='340' side='right'caption='[[4oq3]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4oq3]] is a 4 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=4OQ3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4OQ3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4oq3]] is a 4 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=4OQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OQ3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V8:1-(5-CHLORO-2-METHYLPHENYL)-5-(3-CHLOROPHENYL)-2-(3-METHYLPHENYL)-1H-IMIDAZOLE-4-CARBOXYLIC+ACID'>2V8</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2V8:1-(5-CHLORO-2-METHYLPHENYL)-5-(3-CHLOROPHENYL)-2-(3-METHYLPHENYL)-1H-IMIDAZOLE-4-CARBOXYLIC+ACID'>2V8</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dij\|4dij]]</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=4oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq3 OCA], [https://pdbe.org/4oq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oq3 RCSB], [https://www.ebi.ac.uk/pdbsum/4oq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oq3 ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM2 ([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=4oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq3 OCA], [~~http~~://pdbe.org/4oq3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4oq3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4oq3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4oq3 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.	+	[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>	+	[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4oq3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4oq3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[MDM2 3D structures\|MDM2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Kallen, J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Inhibitor complex]]~~	+	[[Category: Kallen J]]
-	~~[[Category: Ligase-ligase inhibitor complex]]~~	+
-	~~[[Category: Ppi with p53~~]]	+

OCA at 08:29, 22 November 2017

OCA — Wed, 22 Nov 2017 08:29:06 GMT

←Older revision		Revision as of 08:29, 22 November 2017
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 4oq3" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4oq3" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[MDM2\|MDM2]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:29, 11 August 2016

OCA — Thu, 11 Aug 2016 10:29:57 GMT

←Older revision		Revision as of 10:29, 11 August 2016
Line 1:		Line 1:
		+
	==Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction==		==Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction==
	<StructureSection load='4oq3' size='340' side='right' caption='[[4oq3]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4oq3' size='340' side='right' caption='[[4oq3]], [[Resolution\|resolution]] 2.30Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dij\|4dij]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dij\|4dij]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM2 ([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=4oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oq3 RCSB], [http://www.ebi.ac.uk/pdbsum/4oq3 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=4oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq3 OCA], [http://pdbe.org/4oq3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oq3 RCSB], [http://www.ebi.ac.uk/pdbsum/4oq3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oq3 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4oq3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[MDM2\|MDM2]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:44, 5 January 2015

OCA — Mon, 05 Jan 2015 09:44:16 GMT

←Older revision

Revision as of 09:44, 5 January 2015

OCA at 06:45, 21 May 2014

OCA — Wed, 21 May 2014 06:45:37 GMT

←Older revision		Revision as of 06:45, 21 May 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4oq3\| PDB=4oq3 \| SCENE= }}~~	+	==Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction==
-	===Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction===	+	<StructureSection load='4oq3' size='340' side='right' caption='[[4oq3]], [[Resolution\|resolution]] 2.30Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24704029}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4oq3]] is a 4 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=4OQ3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OQ3 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V8:1-(5-CHLORO-2-METHYLPHENYL)-5-(3-CHLOROPHENYL)-2-(3-METHYLPHENYL)-1H-IMIDAZOLE-4-CARBOXYLIC+ACID'>2V8</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dij\|4dij]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oq3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oq3 RCSB], [http://www.ebi.ac.uk/pdbsum/4oq3 PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.		[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
-		+	== Function ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>		[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Capitalizing on crystal structure information obtained from a previous effort in the search for non peptide inhibitors of the p53-MDM2 interaction, we have discovered another new class of compounds able to disrupt this protein-protein interaction, an important target in oncology drug research. The new inhibitors, based on a tetra-substituted imidazole scaffold, have been optimized to low nanomolar potency in a biochemical assay following a structure-guided approach. An appropriate strategy has allowed us to translate the high biochemical potency in significant anti-proliferative activity on a p53-dependent MDM2 amplified cell line.

-	~~==About this Structure==~~	+	Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction.,Vaupel A, Bold G, De Pover A, Stachyra-Valat T, Hergovich-Lisztwan J, Kallen J, Masuya K, Furet P Bioorg Med Chem Lett. 2014 May 1;24(9):2110-4. doi: 10.1016/j.bmcl.2014.03.039., Epub 2014 Mar 22. PMID:24704029<ref>PMID:24704029</ref>
-	~~[[4oq3]] is~~ a 4 ~~chain structure~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.ac.~~il/oca-bin/ocashort?id=4OQ3 OCA]~~.	+

-	==~~Reference~~==	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024704029</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Kallen, J.]]		[[Category: Kallen, J.]]
	[[Category: Inhibitor complex]]		[[Category: Inhibitor complex]]
	[[Category: Ligase-ligase inhibitor complex]]		[[Category: Ligase-ligase inhibitor complex]]
	[[Category: Ppi with p53]]		[[Category: Ppi with p53]]

OCA at 07:39, 23 April 2014

OCA — Wed, 23 Apr 2014 07:39:46 GMT

←Older revision		Revision as of 07:39, 23 April 2014
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4oq3\| PDB=4oq3 \| SCENE= }}
		+	===Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction===
		+	{{ABSTRACT_PUBMED_24704029}}

-	~~The entry 4oq3 is ON HOLD until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.

-	~~Authors~~: ~~Kallen~~, J.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>

-	~~Description~~: ~~Tetra~~-~~substituted imidazoles as a new class of inhibitors of the p53~~-~~MDM2 interaction~~	+	==About this Structure==
		+	[[4oq3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OQ3 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024704029</ref><references group="xtra"/><references/>
		+	[[Category: Kallen, J.]]
		+	[[Category: Inhibitor complex]]
		+	[[Category: Ligase-ligase inhibitor complex]]
		+	[[Category: Ppi with p53]]

OCA at 12:19, 12 March 2014

OCA — Wed, 12 Mar 2014 12:19:04 GMT

←Older revision		Revision as of 12:19, 12 March 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4oq3 is ON HOLD	+	The entry 4oq3 is ON HOLD until Paper Publication

	Authors: Kallen, J.		Authors: Kallen, J.

	Description: Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction		Description: Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction

OCA: Protected "4oq3" [edit=sysop:move=sysop]

OCA — Wed, 19 Feb 2014 16:18:50 GMT

Protected "4oq3" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:18, 19 February 2014

OCA: New page: '''Unreleased structure''' The entry 4oq3 is ON HOLD Authors: Kallen, J. Description: Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction

OCA — Wed, 19 Feb 2014 16:18:49 GMT

New page: '''Unreleased structure''' The entry 4oq3 is ON HOLD Authors: Kallen, J. Description: Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction

New page

'''Unreleased structure'''

The entry 4oq3 is ON HOLD

Authors: Kallen, J.

Description: Tetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction