2hdp - Revision history

OCA at 19:01, 29 May 2024

2024-05-29T19:01:35Z

←Older revision		Revision as of 19:01, 29 May 2024
Line 1:		Line 1:

	==Solution Structure of Hdm2 RING Finger Domain==		==Solution Structure of Hdm2 RING Finger Domain==
-	<StructureSection load='2hdp' size='340' side='right'caption='[[2hdp~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>	+	<StructureSection load='2hdp' size='340' side='right'caption='[[2hdp]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HDP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HDP FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<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">Solution NMR</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~MDM2 ([https~~:/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [https://pdbe.org/2hdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [https://www.ebi.ac.uk/pdbsum/2hdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hdp 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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [https://pdbe.org/2hdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [https://www.ebi.ac.uk/pdbsum/2hdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hdp 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 38:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Dyson~~, H J~~]]	+	[[Category: Dyson HJ]]
-	[[Category: Kostic, M]]	+	[[Category: Kostic M]]
-	[[Category: Matt, T]]	+	[[Category: Matt T]]
-	[[Category: Wright~~, P E~~]]	+	[[Category: Wright PE]]
-	[[Category: Yamout-Martinez, M]]	+	[[Category: Yamout-Martinez M]]
-	~~[[Category: Homodimer]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Ring finger domain~~]]	+

OCA at 07:37, 17 March 2021

2021-03-17T07:37:10Z

←Older revision		Revision as of 07:37, 17 March 2021
Line 1:		Line 1:

	==Solution Structure of Hdm2 RING Finger Domain==		==Solution Structure of Hdm2 RING Finger Domain==
-	<StructureSection load='2hdp' size='340' side='right' caption='[[2hdp]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>	+	<StructureSection load='2hdp' size='340' side='right'caption='[[2hdp]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2HDP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HDP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=ZN:ZINC+ION'>ZN</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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM2 ([https://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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [~~http~~://pdbe.org/2hdp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2hdp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2hdp 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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [https://pdbe.org/2hdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [https://www.ebi.ac.uk/pdbsum/2hdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hdp 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 33:		Line 33:

	==See Also==		==See Also==
-	*[[MDM2\|MDM2]]	+	*[[MDM2 3D structures\|MDM2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 39:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Dyson, H J]]		[[Category: Dyson, H J]]
	[[Category: Kostic, M]]		[[Category: Kostic, M]]

OCA at 06:26, 27 June 2018

2018-06-27T06:26:17Z

←Older revision		Revision as of 06:26, 27 June 2018
Line 1:		Line 1:
		+
	==Solution Structure of Hdm2 RING Finger Domain==		==Solution Structure of Hdm2 RING Finger Domain==
	<StructureSection load='2hdp' size='340' side='right' caption='[[2hdp]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2hdp' size='340' side='right' caption='[[2hdp]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=ZN:ZINC+ION'>ZN</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='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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [http://pdbe.org/2hdp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [http://www.ebi.ac.uk/pdbsum/2hdp 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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [http://pdbe.org/2hdp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [http://www.ebi.ac.uk/pdbsum/2hdp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hdp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/2hdp_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hd/2hdp_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 02:29, 8 February 2016

2016-02-08T02:29:36Z

←Older revision		Revision as of 02:29, 8 February 2016
Line 19:		Line 19:
	<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=2hdp ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:00, 10 September 2015

2015-09-10T07:00:57Z

←Older revision		Revision as of 07:00, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='2hdp' size='340' side='right' caption='[[2hdp]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>		<StructureSection load='2hdp' size='340' side='right' caption='[[2hdp]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HDP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HDP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=ZN:ZINC+ION'>ZN</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 ~~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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [http://www.ebi.ac.uk/pdbsum/2hdp 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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [http://pdbe.org/2hdp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [http://www.ebi.ac.uk/pdbsum/2hdp PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 29:		Line 29:
	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 2hdp" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Dyson, H J]]		[[Category: Dyson, H J]]
	[[Category: Kostic, M]]		[[Category: Kostic, M]]

OCA at 08:13, 16 January 2015

2015-01-16T08:13:24Z

←Older revision		Revision as of 08:13, 16 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HDP FirstGlance]. <br>		<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HDP FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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 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 Homo sapiens])</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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [http://www.ebi.ac.uk/pdbsum/2hdp 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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [http://www.ebi.ac.uk/pdbsum/2hdp 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 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Dyson, H J.]]	+	[[Category: Dyson, H J]]
-	[[Category: Kostic, M.]]	+	[[Category: Kostic, M]]
-	[[Category: Matt, T.]]	+	[[Category: Matt, T]]
-	[[Category: Wright, P E.]]	+	[[Category: Wright, P E]]
-	[[Category: Yamout-Martinez, M.]]	+	[[Category: Yamout-Martinez, M]]
	[[Category: Homodimer]]		[[Category: Homodimer]]
	[[Category: Ligase]]		[[Category: Ligase]]
	[[Category: Ring finger domain]]		[[Category: Ring finger domain]]

OCA at 07:54, 30 September 2014

2014-09-30T07:54:30Z

←Older revision		Revision as of 07:54, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2hdp\| PDB=2hdp \| SCENE= }}~~	+	==Solution Structure of Hdm2 RING Finger Domain==
-	===Solution Structure of Hdm2 RING Finger Domain===	+	<StructureSection load='2hdp' size='340' side='right' caption='[[2hdp]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_16965791}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[2hdp]] is a 2 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=2HDP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HDP FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
		+	<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 Homo sapiens])</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=2hdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hdp RCSB], [http://www.ebi.ac.uk/pdbsum/2hdp 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/hd/2hdp_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 ==
		+	Regulation of the transcriptional response to the tumor suppressor p53 occurs at many levels, including control of its transcriptional activity, and of its stability and concentration within the cell. p53 stability is regulated by the protein Hdm2, an E3 ubiquitin ligase that binds to p53 and promotes its ubiquitination and degradation. The C-terminal domain of Hdm2, which is critical for this activity, has been classified as a RING domain on the basis of sequence homology, although it lacks the canonical set of zinc ligands (RING domains typically have C3HC4 or C4C4 zinc coordination). Here, we report the solution structure of the C2H2C4 RING domain of Hdm2(429-491), which reveals a symmetrical dimer with a unique cross-brace zinc-binding scheme. Each subunit has one Cys4 Zn site and one His2Cys2 Zn site. The global fold of each subunit is similar to those reported for other RING domains, with a compact betabetaalphabeta fold, a small hydrophobic core, and two Zn ions, which are essential for maintaining the domain structure. The dimer structure is maintained by an extensive interface that buries a large hydrophobic area on each subunit. It has been proposed that Hdm2 and its homologue HdmX form a stable heterodimer through their RING domains, resulting in a synergistic increase in observed E3 activity. To test this proposal, we prepared an HdmX RING construct and showed by NMR titration that it forms a tight 1:1 complex with the Hdm2 RING. The resonances most perturbed by heterodimer formation are located within the subunit interface of the homodimer, far removed from the surface expected to form the docking site of the E2 ubiquitin-conjugating enzyme, providing a structure-based rationale for the function of the RING domains in p53 ubiquitination.

-	~~==Function==~~	+	Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination of p53.,Kostic M, Matt T, Martinez-Yamout MA, Dyson HJ, Wright PE J Mol Biol. 2006 Oct 20;363(2):433-50. Epub 2006 Aug 14. PMID:16965791<ref>PMID:16965791</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>
-	~~[[2hdp]] is~~ a ~~2 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=2HDP OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[MDM2\|MDM2]]		*[[MDM2\|MDM2]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:016965791</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Dyson, H J.]]		[[Category: Dyson, H J.]]

OCA at 03:30, 25 March 2013

2013-03-25T03:30:38Z

←Older revision		Revision as of 03:30, 25 March 2013
Line 1:		Line 1:
-	[[Image:2hdp.png\|left\|200px]]
-
	{{STRUCTURE_2hdp\| PDB=2hdp \| SCENE= }}		{{STRUCTURE_2hdp\| PDB=2hdp \| SCENE= }}
-
	===Solution Structure of Hdm2 RING Finger Domain===		===Solution Structure of Hdm2 RING Finger Domain===
		+	{{ABSTRACT_PUBMED_16965791}}

-	~~{{ABSTRACT_PUBMED_16965791}}~~	+	==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:016965791</ref><references group="xtra"/>	+	<ref group="xtra">PMID:016965791</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Dyson, H J.]]		[[Category: Dyson, H J.]]

OCA at 08:36, 20 October 2012

2012-10-20T08:36:00Z

←Older revision		Revision as of 08:36, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2hdp]] is a 2 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=2HDP OCA].	+	[[2hdp]] is a 2 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=2HDP OCA].

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

OCA: Protected "2hdp" [edit=sysop:move=sysop]

2012-07-25T20:03:37Z

Protected "2hdp" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:03, 25 July 2012