3lbl - Revision history

OCA at 16:22, 1 November 2023

OCA — Wed, 01 Nov 2023 16:22:44 GMT

←Older revision		Revision as of 16:22, 1 November 2023
Line 1:		Line 1:

	==Structure of human MDM2 protein in complex with Mi-63-analog==		==Structure of human MDM2 protein in complex with Mi-63-analog==
-	<StructureSection load='3lbl' size='340' side='right' caption='[[3lbl]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='3lbl' size='340' side='right'caption='[[3lbl]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lbl]] is a 3 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=3LBL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3LBL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lbl]] is a 3 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=3LBL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LBL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MI6:(2R,3R,4R,5R)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-N-(2-MORPHOLIN-4-YLETHYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>MI6</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]] 1.6Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ycr\|1ycr]], [[3lbj\|3lbj]], [[3lbk\|3lbk]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MI6:(2R,3R,4R,5R)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-N-(2-MORPHOLIN-4-YLETHYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>MI6</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=3lbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbl OCA], [https://pdbe.org/3lbl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lbl RCSB], [https://www.ebi.ac.uk/pdbsum/3lbl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lbl 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=3lbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbl OCA], [~~http~~://pdbe.org/3lbl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3lbl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3lbl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3lbl 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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 33:

	==See Also==		==See Also==
-	*[[MDM2\|MDM2]]	+	*[[MDM2 3D structures\|MDM2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Czarna, A~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Holak, T~~ A]]	+	[[Category: Czarna A]]
-	[[Category: ~~Popowicz, G M~~]]	+	[[Category: Holak TA]]
-	[[Category: ~~Wolf, S~~]]	+	[[Category: Popowicz GM]]
-	[[Category: ~~Alternative splicing]]~~	+	[[Category: Wolf S]]
-	~~[[Category: Cytoplasm]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Mdm2]]~~	+
-	~~[[Category: Mdmx]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: P53]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Proto-oncogene]]~~	+
-	~~[[Category: Ubl conjugation]]~~	+
-	~~[[Category: Ubl conjugation pathway]]~~	+
-	~~[[Category: Zinc-finger~~]]	+

OCA at 08:16, 17 October 2018

OCA — Wed, 17 Oct 2018 08:16:59 GMT

←Older revision		Revision as of 08:16, 17 October 2018
Line 17:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lb/3lbl_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lb/3lbl_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 23:		Line 23:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lbl ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lbl ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Intensive anticancer drug discovery efforts have been made to develop small molecule inhibitors of the p53-MDM2 and p53-MDMX interactions. We present here the structures of the most potent inhibitors bound to MDM2 and MDMX that are based on the new imidazo-indole scaffold. In addition, the structure of the recently reported spiro-oxindole inhibitor bound to MDM2 is described. The structures indicate how the substituents of a small molecule that bind to the three subpockets of the MDM2/X-p53 interaction should be optimized for effective binding to MDM2 and/or MDMX. While the spiro-oxindole inhibitor triggers significant ligand-induced changes in MDM2, the imidazo-indoles share similar binding modes for MDMX and MDM2, but cause only minimal induced-fit changes in the structures of both proteins. Our study includes the first structure of the complex between MDMX and a small molecule and should aid in developing efficient scaffolds for binding to MDMX and/or MDM2.
		+
		+	Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery.,Popowicz GM, Czarna A, Wolf S, Wang K, Wang W, Domling A, Holak TA Cell Cycle. 2010 Mar 15;9(6):1104-11. doi: 10.4161/cc.9.6.10956. Epub 2010 Mar, 15. PMID:20237429<ref>PMID:20237429</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 3lbl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[MDM2\|MDM2]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:53, 1 November 2017

OCA — Wed, 01 Nov 2017 08:53:00 GMT

←Older revision		Revision as of 08:53, 1 November 2017
Line 23:		Line 23:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lbl ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lbl ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-
-	==See Also==
-	*[[MDM2\|MDM2]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 32:
	[[Category: Popowicz, G M]]		[[Category: Popowicz, G M]]
	[[Category: Wolf, S]]		[[Category: Wolf, S]]
		+	[[Category: Alternative splicing]]
		+	[[Category: Cytoplasm]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Ligase]]		[[Category: Ligase]]
Line 43:		Line 42:
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	[[Category: Proto-oncogene]]		[[Category: Proto-oncogene]]
		+	[[Category: Ubl conjugation]]
	[[Category: Ubl conjugation pathway]]		[[Category: Ubl conjugation pathway]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

OCA at 09:09, 4 August 2016

OCA — Thu, 04 Aug 2016 09:09:24 GMT

←Older revision		Revision as of 09:09, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of human MDM2 protein in complex with Mi-63-analog==		==Structure of human MDM2 protein in complex with Mi-63-analog==
	<StructureSection load='3lbl' size='340' side='right' caption='[[3lbl]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='3lbl' size='340' side='right' caption='[[3lbl]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3lbl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LBL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3lbl]] is a 3 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=3LBL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LBL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MI6:(2R,3R,4R,5R)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-N-(2-MORPHOLIN-4-YLETHYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>MI6</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MI6:(2R,3R,4R,5R)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-N-(2-MORPHOLIN-4-YLETHYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>MI6</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ycr\|1ycr]], [[3lbj\|3lbj]], [[3lbk\|3lbk]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ycr\|1ycr]], [[3lbj\|3lbj]], [[3lbk\|3lbk]]</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 ~~Homo sapiens~~])</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=3lbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lbl RCSB], [http://www.ebi.ac.uk/pdbsum/3lbl 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=3lbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbl OCA], [http://pdbe.org/3lbl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lbl RCSB], [http://www.ebi.ac.uk/pdbsum/3lbl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lbl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lbl ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>

Line 29:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Czarna, A]]		[[Category: Czarna, A]]
	[[Category: Holak, T A]]		[[Category: Holak, T A]]

OCA at 16:13, 18 December 2014

OCA — Thu, 18 Dec 2014 16:13:16 GMT

←Older revision		Revision as of 16:13, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3lbl\| PDB=3lbl \| SCENE= }}~~	+	==Structure of human MDM2 protein in complex with Mi-63-analog==
-	===Structure of human MDM2 protein in complex with Mi-63-analog===	+	<StructureSection load='3lbl' size='340' side='right' caption='[[3lbl]], [[Resolution\|resolution]] 1.60Å' scene=''>
-		+	== Structural highlights ==
-	==Disease==	+	<table><tr><td colspan='2'>[[3lbl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LBL FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MI6:(2R,3R,4R,5R)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-N-(2-MORPHOLIN-4-YLETHYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>MI6</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ycr\|1ycr]], [[3lbj\|3lbj]], [[3lbk\|3lbk]]</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 Homo sapiens])</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=3lbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lbl RCSB], [http://www.ebi.ac.uk/pdbsum/3lbl 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>	+	== Evolutionary Conservation ==
-		+	[[Image:Consurf_key_small.gif\|200px\|right]]
-	==~~About this Structure~~==	+	Check<jmol>
-	[[~~3lbl~~]] ~~is a 3 chain~~ structure ~~with sequence from~~ [http://en.~~wikipedia~~.~~org~~/~~wiki/Homo_sapiens Homo sapiens~~]. ~~Full crystallographic information is~~ available from [http://~~oca~~.~~weizmann~~.ac.il/~~oca-bin~~/~~ocashort~~?id=~~3LBL OCA~~].	+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lb/3lbl_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>

	==See Also==		==See Also==
	*[[MDM2\|MDM2]]		*[[MDM2\|MDM2]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Czarna, A.]]	+	[[Category: Czarna, A]]
-	[[Category: Holak, T A.]]	+	[[Category: Holak, T A]]
-	[[Category: Popowicz, G M.]]	+	[[Category: Popowicz, G M]]
-	[[Category: Wolf, S.]]	+	[[Category: Wolf, S]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Ligase]]		[[Category: Ligase]]

OCA at 11:19, 24 March 2013

OCA — Sun, 24 Mar 2013 11:19:45 GMT

←Older revision		Revision as of 11:19, 24 March 2013
Line 1:		Line 1:
-	[[Image:3lbl.png\|left\|200px]]
-
	{{STRUCTURE_3lbl\| PDB=3lbl \| SCENE= }}		{{STRUCTURE_3lbl\| PDB=3lbl \| SCENE= }}
-
	===Structure of human MDM2 protein in complex with Mi-63-analog===		===Structure of human MDM2 protein in complex with Mi-63-analog===

		+	==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.
		+
		+	==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>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:
	==See Also==		==See Also==
	*[[MDM2\|MDM2]]		*[[MDM2\|MDM2]]
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Czarna, A.]]		[[Category: Czarna, A.]]

OCA at 14:17, 20 October 2012

OCA — Sat, 20 Oct 2012 14:17:16 GMT

←Older revision		Revision as of 14:17, 20 October 2012
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[3lbl]] is a 3 chain structure ~~of [[MDM2]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA].	+	[[3lbl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA].

	==See Also==		==See Also==

OCA: Protected "3lbl" [edit=sysop:move=sysop]

OCA — Thu, 26 Jul 2012 14:40:22 GMT

Protected "3lbl" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:40, 26 July 2012

OCA at 14:40, 26 July 2012

OCA — Thu, 26 Jul 2012 14:40:20 GMT

←Older revision		Revision as of 14:40, 26 July 2012
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3lbl.png\|left\|200px]]
-	[[Image:3lbl.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3lbl", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3lbl\| PDB=3lbl \| SCENE= }}		{{STRUCTURE_3lbl\| PDB=3lbl \| SCENE= }}

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	==About this Structure==		==About this Structure==
-	~~3LBL~~ is a 3 ~~chains~~ structure with ~~sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA].	+	[[3lbl]] is a 3 chain structure of [[MDM2]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA].
		+
		+	==See Also==
		+	*[[MDM2\|MDM2]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Czarna, A.]]		[[Category: Czarna, A.]]
Line 20:		Line 16:
	[[Category: Popowicz, G M.]]		[[Category: Popowicz, G M.]]
	[[Category: Wolf, S.]]		[[Category: Wolf, S.]]
-	[[Category: Alternative splicing]]
-	[[Category: Cytoplasm]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Ligase]]		[[Category: Ligase]]
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	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
	[[Category: Proto-oncogene]]		[[Category: Proto-oncogene]]
-	[[Category: Ubl conjugation]]
	[[Category: Ubl conjugation pathway]]		[[Category: Ubl conjugation pathway]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 17 09:43:46 2010''

OCA at 07:43, 17 March 2010

OCA — Wed, 17 Mar 2010 07:43:47 GMT

←Older revision		Revision as of 07:43, 17 March 2010
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3lbl.jpg\|left\|200px]]

-	The ~~entry 3lbl~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3lbl", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3lbl\| PDB=3lbl \| SCENE= }}

-	~~Authors: Popowicz, G.M., Czarna, A., Wolf, S., Holak, T.A.~~	+	===Structure of human MDM2 protein in complex with Mi-63-analog===

-	Description: Structure of human MDM2 protein in complex with Mi-63-analog

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Feb 3~~ 09:18:40 2010''	+	==About this Structure==
		+	3LBL is a 3 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Czarna, A.]]
		+	[[Category: Holak, T A.]]
		+	[[Category: Popowicz, G M.]]
		+	[[Category: Wolf, S.]]
		+	[[Category: Alternative splicing]]
		+	[[Category: Cytoplasm]]
		+	[[Category: Inhibitor]]
		+	[[Category: Ligase]]
		+	[[Category: Mdm2]]
		+	[[Category: Mdmx]]
		+	[[Category: Nucleus]]
		+	[[Category: P53]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Proto-oncogene]]
		+	[[Category: Ubl conjugation]]
		+	[[Category: Ubl conjugation pathway]]
		+	[[Category: Zinc-finger]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 17 09:43:46 2010''