4oba - Revision history

OCA at 17:09, 20 September 2023

2023-09-20T17:09:10Z

←Older revision		Revision as of 17:09, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4oba]] 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=4OBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OBA FirstGlance]. <br>		<table><tr><td colspan='2'>[[4oba]] 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=4OBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OBA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TW:[(2R,5R,6R)-4-[(1S)-2-(TERT-BUTYLSULFONYL)-1-CYCLOPROPYLETHYL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TW</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]] 1.602Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TW:[(2R,5R,6R)-4-[(1S)-2-(TERT-BUTYLSULFONYL)-1-CYCLOPROPYLETHYL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TW</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=4oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oba OCA], [https://pdbe.org/4oba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oba RCSB], [https://www.ebi.ac.uk/pdbsum/4oba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oba 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=4oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oba OCA], [https://pdbe.org/4oba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oba RCSB], [https://www.ebi.ac.uk/pdbsum/4oba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oba ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:15, 25 January 2023

2023-01-25T07:15:35Z

←Older revision		Revision as of 07:15, 25 January 2023
Line 1:		Line 1:

	==Co-crystal structure of MDM2 with Inhibitor Compound 4==		==Co-crystal structure of MDM2 with Inhibitor Compound 4==
-	<StructureSection load='4oba' size='340' side='right' caption='[[4oba]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='4oba' size='340' side='right'caption='[[4oba]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4oba]] 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=4OBA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4OBA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4oba]] 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=4OBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OBA FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2TW:[(2R,5R,6R)-4-[(1S)-2-(TERT-BUTYLSULFONYL)-1-CYCLOPROPYLETHYL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TW</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TW:[(2R,5R,6R)-4-[(1S)-2-(TERT-BUTYLSULFONYL)-1-CYCLOPROPYLETHYL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TW</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=4oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oba OCA], [https://pdbe.org/4oba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oba RCSB], [https://www.ebi.ac.uk/pdbsum/4oba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oba 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=4oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oba OCA], [~~http~~://pdbe.org/4oba PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4oba RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4oba PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4oba ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.	+	[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>	+	[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:

	==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: ~~Huang, X~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Long, A M~~]]	+	[[Category: Huang X]]
-	[[Category: ~~Shaffer, P L~~]]	+	[[Category: Long AM]]
-	[[Category: ~~Yakowec, P~~]]	+	[[Category: Shaffer PL]]
-	[[Category: ~~Ligase-ligase inhibitor complex]]~~	+	[[Category: Yakowec P]]
-	~~[[Category: P53]]~~	+
-	~~[[Category: Protein-protein interaction~~]]	+

OCA at 14:21, 11 August 2016

2016-08-11T14:21:19Z

←Older revision		Revision as of 14:21, 11 August 2016
Line 1:		Line 1:
		+
	==Co-crystal structure of MDM2 with Inhibitor Compound 4==		==Co-crystal structure of MDM2 with Inhibitor Compound 4==
	<StructureSection load='4oba' size='340' side='right' caption='[[4oba]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4oba' size='340' side='right' caption='[[4oba]], [[Resolution\|resolution]] 1.60Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2TW:[(2R,5R,6R)-4-[(1S)-2-(TERT-BUTYLSULFONYL)-1-CYCLOPROPYLETHYL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TW</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2TW:[(2R,5R,6R)-4-[(1S)-2-(TERT-BUTYLSULFONYL)-1-CYCLOPROPYLETHYL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TW</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=4oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oba OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oba RCSB], [http://www.ebi.ac.uk/pdbsum/4oba 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=4oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oba OCA], [http://pdbe.org/4oba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oba RCSB], [http://www.ebi.ac.uk/pdbsum/4oba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oba ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4oba" style="background-color:#fffaf0;"></div>

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

OCA at 08:39, 5 January 2015

2015-01-05T08:39:07Z

←Older revision		Revision as of 08:39, 5 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4oba\| PDB=4oba \| SCENE= }}~~	+	==Co-crystal structure of MDM2 with Inhibitor Compound 4==
-	===Co-crystal structure of MDM2 with Inhibitor Compound 4===	+	<StructureSection load='4oba' size='340' side='right' caption='[[4oba]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24548297}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4oba]] 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=4OBA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OBA FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2TW:[(2R,5R,6R)-4-[(1S)-2-(TERT-BUTYLSULFONYL)-1-CYCLOPROPYLETHYL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TW</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4oba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oba OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oba RCSB], [http://www.ebi.ac.uk/pdbsum/4oba PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.		[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
-		+	== Function ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>		[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We previously reported the discovery of AMG 232, a highly potent and selective piperidinone inhibitor of the MDM2-p53 interaction. Our continued search for potent and diverse analogues led to the discovery of novel morpholinone MDM2 inhibitors. This change to a morpholinone core has a significant impact on both potency and metabolic stability compared to the piperidinone series. Within this morpholinone series, AM-8735 emerged as an inhibitor with remarkable biochemical potency (HTRF IC50 = 0.4 nM) and cellular potency (SJSA-1 EdU IC50 = 25 nM), as well as pharmacokinetic properties. Compound 4 also shows excellent antitumor activity in the SJSA-1 osteosarcoma xenograft model with an ED50 of 41 mg/kg. Lead optimization toward the discovery of this inhibitor as well as key differences between the morpholinone and the piperidinone series will be described herein.

-	~~==About this Structure==~~	+	Selective and Potent Morpholinone Inhibitors of the MDM2-p53 Protein-Protein Interaction.,Gonzalez AZ, Eksterowicz J, Bartberger MD, Beck HP, Canon J, Chen A, Chow D, Duquette J, Fox BM, Fu J, Huang X, Houze JB, Jin L, Li Y, Li Z, Ling Y, Lo MC, Long AM, McGee LR, McIntosh J, McMinn DL, Oliner JD, Osgood T, Rew Y, Saiki AY, Shaffer P, Wortman S, Yakowec P, Yan X, Ye Q, Yu D, Zhao X, Zhou J, Olson SH, Medina JC, Sun D J Med Chem. 2014 Mar 4. PMID:24548297<ref>PMID:24548297</ref>
-	~~[[4oba]] is a 3 chain structure~~. ~~Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=4OBA OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[MDM2\|MDM2]]		*[[MDM2\|MDM2]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:024548297</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
-	[[Category: Huang, X.]]	+	</StructureSection>
-	[[Category: Long, A M.]]	+	[[Category: Human]]
-	[[Category: Shaffer, P L.]]	+	[[Category: Huang, X]]
-	[[Category: Yakowec, P.]]	+	[[Category: Long, A M]]
		+	[[Category: Shaffer, P L]]
		+	[[Category: Yakowec, P]]
	[[Category: Ligase-ligase inhibitor complex]]		[[Category: Ligase-ligase inhibitor complex]]
	[[Category: P53]]		[[Category: P53]]
	[[Category: Protein-protein interaction]]		[[Category: Protein-protein interaction]]

OCA at 04:21, 9 April 2014

2014-04-09T04:21:35Z

←Older revision		Revision as of 04:21, 9 April 2014
Line 11:		Line 11:
	==About this Structure==		==About this Structure==
	[[4oba]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OBA OCA].		[[4oba]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OBA OCA].
		+
		+	==See Also==
		+	*[[MDM2\|MDM2]]

	==Reference==		==Reference==

OCA at 08:41, 19 March 2014

2014-03-19T08:41:24Z

←Older revision		Revision as of 08:41, 19 March 2014
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4oba\| PDB=4oba \| SCENE= }}
		+	===Co-crystal structure of MDM2 with Inhibitor Compound 4===
		+	{{ABSTRACT_PUBMED_24548297}}

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

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

-	~~Description~~: Co-~~crystal structure of MDM2 with Inhibitor Compound 4~~	+	==About this Structure==
		+	[[4oba]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OBA OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024548297</ref><references group="xtra"/><references/>
		+	[[Category: Huang, X.]]
		+	[[Category: Long, A M.]]
		+	[[Category: Shaffer, P L.]]
		+	[[Category: Yakowec, P.]]
		+	[[Category: Ligase-ligase inhibitor complex]]
		+	[[Category: P53]]
		+	[[Category: Protein-protein interaction]]

OCA at 04:49, 13 February 2014

2014-02-13T04:49:54Z

←Older revision		Revision as of 04:49, 13 February 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Shaffer, P.L., Huang, X., Yakowec, P., Long, A.M.		Authors: Shaffer, P.L., Huang, X., Yakowec, P., Long, A.M.

	Description: Co-crystal structure of MDM2 with Inhibitor Compound 4		Description: Co-crystal structure of MDM2 with Inhibitor Compound 4

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

2014-01-15T07:44:55Z

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

←Older revision

Revision as of 07:44, 15 January 2014

OCA: New page: '''Unreleased structure''' The entry 4oba is ON HOLD Authors: Shaffer, P.L., Huang, X., Yakowec, P., Long, A.M. Description: Co-crystal structure of MDM2 with Inhibitor Compound 4

2014-01-15T07:44:53Z

New page: '''Unreleased structure''' The entry 4oba is ON HOLD Authors: Shaffer, P.L., Huang, X., Yakowec, P., Long, A.M. Description: Co-crystal structure of MDM2 with Inhibitor Compound 4

New page

'''Unreleased structure'''

The entry 4oba is ON HOLD

Authors: Shaffer, P.L., Huang, X., Yakowec, P., Long, A.M.

Description: Co-crystal structure of MDM2 with Inhibitor Compound 4