1z1m - Revision history

OCA at 08:08, 15 May 2024

OCA — Wed, 15 May 2024 08:08:08 GMT

←Older revision		Revision as of 08:08, 15 May 2024
Line 1:		Line 1:

	==NMR structure of unliganded MDM2==		==NMR structure of unliganded MDM2==
-	<StructureSection load='1z1m' size='340' side='right'caption='[[1z1m~~]], [[NMR_Ensembles_of_Models \| 24 NMR models~~]]' scene=''>	+	<StructureSection load='1z1m' size='340' side='right'caption='[[1z1m]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>
-	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [https://pdbe.org/1z1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [https://www.ebi.ac.uk/pdbsum/1z1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z1m ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [https://pdbe.org/1z1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [https://www.ebi.ac.uk/pdbsum/1z1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z1m ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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.	+	[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 ==
-	[[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>	+	[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 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Barlow~~, P N~~]]	+	[[Category: Barlow PN]]
-	[[Category: Fischer, P]]	+	[[Category: Fischer P]]
-	[[Category: McInnes, C]]	+	[[Category: McInnes C]]
-	[[Category: Powers, H]]	+	[[Category: Powers H]]
-	[[Category: Uhrin, D]]	+	[[Category: Uhrin D]]
-	[[Category: Uhrinova, S]]	+	[[Category: Uhrinova S]]
-	[[Category: Watt, K]]	+	[[Category: Watt K]]
-	[[Category: Zheleva, D]]	+	[[Category: Zheleva D]]
-	~~[[Category: Alpha-beta domain]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Peptide-binding groove]]~~	+
-	~~[[Category: Psudosymmetry~~]]	+

OCA at 16:35, 3 November 2021

OCA — Wed, 03 Nov 2021 16:35:43 GMT

←Older revision		Revision as of 16:35, 3 November 2021
Line 3:		Line 3:
	<StructureSection load='1z1m' size='340' side='right'caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>		<StructureSection load='1z1m' size='340' side='right'caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>
-	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [~~http~~://pdbe.org/1z1m PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1z1m PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1z1m ProSAT]</span></td></tr>	+	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [https://pdbe.org/1z1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [https://www.ebi.ac.uk/pdbsum/1z1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z1m 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]]

OCA at 17:12, 29 January 2020

OCA — Wed, 29 Jan 2020 17:12:27 GMT

←Older revision		Revision as of 17:12, 29 January 2020
Line 1:		Line 1:

	==NMR structure of unliganded MDM2==		==NMR structure of unliganded MDM2==
-	<StructureSection load='1z1m' size='340' side='right' caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>	+	<StructureSection load='1z1m' size='340' side='right'caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>		<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>
Line 31:		Line 31:

	==See Also==		==See Also==
-	*[[MDM2\|MDM2]]	+	*[[MDM2 3D structures\|MDM2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Barlow, P N]]		[[Category: Barlow, P N]]
	[[Category: Fischer, P]]		[[Category: Fischer, P]]

OCA at 06:54, 25 April 2018

OCA — Wed, 25 Apr 2018 06:54:45 GMT

←Older revision		Revision as of 06:54, 25 April 2018
Line 1:		Line 1:
		+
	==NMR structure of unliganded MDM2==		==NMR structure of unliganded MDM2==
	<StructureSection load='1z1m' size='340' side='right' caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>		<StructureSection load='1z1m' size='340' side='right' caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>		<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>
-	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [http://pdbe.org/1z1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [http://www.ebi.ac.uk/pdbsum/1z1m PDBsum]</span></td></tr>	+	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [http://pdbe.org/1z1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [http://www.ebi.ac.uk/pdbsum/1z1m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1z1m ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z1/1z1m_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z1/1z1m_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>

OCA at 15:30, 9 February 2016

OCA — Tue, 09 Feb 2016 15:30:47 GMT

←Older revision		Revision as of 15:30, 9 February 2016
Line 17:		Line 17:
	<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=1z1m ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 23:36, 10 September 2015

OCA — Thu, 10 Sep 2015 23:36:17 GMT

←Older revision		Revision as of 23:36, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1z1m' size='340' side='right' caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>		<StructureSection load='1z1m' size='340' side='right' caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>
-	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [http://www.ebi.ac.uk/pdbsum/1z1m PDBsum]</span></td></tr>	+	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [http://pdbe.org/1z1m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [http://www.ebi.ac.uk/pdbsum/1z1m PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 27:		Line 27:
	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 1z1m" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Barlow, P N]]		[[Category: Barlow, P N]]
	[[Category: Fischer, P]]		[[Category: Fischer, P]]

OCA at 10:30, 8 January 2015

OCA — Thu, 08 Jan 2015 10:30:11 GMT

←Older revision		Revision as of 10:30, 8 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>		<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>
-	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [http://www.ebi.ac.uk/pdbsum/1z1m PDBsum]</span></td></tr>	+	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [http://www.ebi.ac.uk/pdbsum/1z1m PDBsum]</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.		[[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.
Line 35:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Barlow, P N.]]	+	[[Category: Barlow, P N]]
-	[[Category: Fischer, P.]]	+	[[Category: Fischer, P]]
-	[[Category: McInnes, C.]]	+	[[Category: McInnes, C]]
-	[[Category: Powers, H.]]	+	[[Category: Powers, H]]
-	[[Category: Uhrin, D.]]	+	[[Category: Uhrin, D]]
-	[[Category: Uhrinova, S.]]	+	[[Category: Uhrinova, S]]
-	[[Category: Watt, K.]]	+	[[Category: Watt, K]]
-	[[Category: Zheleva, D.]]	+	[[Category: Zheleva, D]]
	[[Category: Alpha-beta domain]]		[[Category: Alpha-beta domain]]
	[[Category: Ligase]]		[[Category: Ligase]]
	[[Category: Peptide-binding groove]]		[[Category: Peptide-binding groove]]
	[[Category: Psudosymmetry]]		[[Category: Psudosymmetry]]

OCA at 19:10, 29 September 2014

OCA — Mon, 29 Sep 2014 19:10:26 GMT

←Older revision		Revision as of 19:10, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1z1m\| PDB~~=1z1m \| ~~SCENE~~= }}	+	==NMR structure of unliganded MDM2==
-	===~~NMR structure of unliganded MDM2~~===	+	<StructureSection load='1z1m' size='340' side='right' caption='[[1z1m]], [[NMR_Ensembles_of_Models \| 24 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_15953616}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Z1M FirstGlance]. <br>
-	==Disease==	+	</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=1z1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z1m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1z1m RCSB], [http://www.ebi.ac.uk/pdbsum/1z1m 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 ==
		+	[[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]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z1/1z1m_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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Critical to the inhibitory action of the oncogene product, MDM2, on the tumour suppressor, p53, is association of the N-terminal domain of MDM2 (MDM2N) with the transactivation domain of p53. The structure of MDM2N was previously solved with a p53-derived peptide, or small-molecule ligands, occupying its binding cleft, but no structure of the non-liganded MDM2N (i.e. the apo-form) has been reported. Here, we describe the solution structure and dynamics of apo-MDM2N and thus reveal the nature of the conformational changes in MDM2N that accompany binding of p53. The new structure suggests that p53 effects displacement of an N-terminal segment of apo-MDM2N that occludes access to the shallow end of the p53-binding cleft. MDM2N must also undergo an expansion upon binding, achieved through a rearrangement of its two pseudosymetrically related sub-domains resulting in outward displacements of the secondary structural elements that comprise the walls and floor of the p53-binding cleft. MDM2N becomes more rigid and stable upon binding p53. Conformational plasticity of the binding cleft of apo-MDM2N could allow the parent protein to bind specifically to several different partners, although, to date, all the known liganded structures of MDM2N are highly similar to one another. The results indicate that the more open conformation of the binding cleft of MDM2N observed in structures of complexes with small molecules and peptides is a more suitable one for ligand discovery and optimisation.

-	~~==Function==~~	+	Structure of free MDM2 N-terminal domain reveals conformational adjustments that accompany p53-binding.,Uhrinova S, Uhrin D, Powers H, Watt K, Zheleva D, Fischer P, McInnes C, Barlow PN J Mol Biol. 2005 Jul 15;350(3):587-98. PMID:15953616<ref>PMID:15953616</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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[1z1m]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full experimental information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[MDM2\|MDM2]]		*[[MDM2\|MDM2]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:015953616</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Barlow, P N.]]		[[Category: Barlow, P N.]]

OCA at 11:30, 24 March 2013

OCA — Sun, 24 Mar 2013 11:30:25 GMT

←Older revision		Revision as of 11:30, 24 March 2013
Line 1:		Line 1:
-	[[Image:1z1m.png\|left\|200px]]
-
	{{STRUCTURE_1z1m\| PDB=1z1m \| SCENE= }}		{{STRUCTURE_1z1m\| PDB=1z1m \| SCENE= }}
-
	===NMR structure of unliganded MDM2===		===NMR structure of unliganded MDM2===
		+	{{ABSTRACT_PUBMED_15953616}}

-	~~{{ABSTRACT_PUBMED_15953616}}~~	+	==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 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:015953616</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015953616</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Barlow, P N.]]		[[Category: Barlow, P N.]]

OCA at 14:18, 20 October 2012

OCA — Sat, 20 Oct 2012 14:18:47 GMT

←Older revision		Revision as of 14:18, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1z1m]] is a 1 chain structure ~~of [[MDM2]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA].	+	[[1z1m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z1M OCA].

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