3w69 - Revision history

OCA at 12:51, 8 November 2023

OCA — Wed, 08 Nov 2023 12:51:58 GMT

←Older revision		Revision as of 12:51, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='3w69' size='340' side='right'caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3w69' size='340' side='right'caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3w69]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W69 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3w69]] is a 2 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=3W69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W69 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.9Å</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=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [https://pdbe.org/3w69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [https://www.ebi.ac.uk/pdbsum/3w69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w69 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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [https://pdbe.org/3w69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [https://www.ebi.ac.uk/pdbsum/3w69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w69 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Katakura, S]]	+	[[Category: Katakura S]]
-	[[Category: Kawato, H]]	+	[[Category: Kawato H]]
-	[[Category: Miyazaki, M]]	+	[[Category: Miyazaki M]]
-	[[Category: Naito, H]]	+	[[Category: Naito H]]
-	[[Category: Okayama, T]]	+	[[Category: Okayama T]]
-	[[Category: Shimizu, H]]	+	[[Category: Shimizu H]]
-	[[Category: Soga, T]]	+	[[Category: Soga T]]
-	[[Category: Sugimoto, Y]]	+	[[Category: Sugimoto Y]]
-	~~[[Category: Ligase-ligase inhibitor complex]]~~	+
-	~~[[Category: P53]]~~	+
-	~~[[Category: Ubiquitin-protein ligase e3 mdm2~~]]	+

OCA at 05:24, 3 August 2022

OCA — Wed, 03 Aug 2022 05:24:01 GMT

←Older revision		Revision as of 05:24, 3 August 2022
Line 1:		Line 1:

	==Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor==		==Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor==
-	<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='3w69' size='340' side='right'caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3w69]] is a 2 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=3W69 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3W69 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3w69]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W69 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [~~http~~://pdbe.org/3w69 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3w69 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3w69 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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [https://pdbe.org/3w69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [https://www.ebi.ac.uk/pdbsum/3w69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w69 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 23:

	==See Also==		==See Also==
-	*[[MDM2\|MDM2]]	+	*[[MDM2 3D structures\|MDM2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Katakura, S]]		[[Category: Katakura, S]]
	[[Category: Kawato, H]]		[[Category: Kawato, H]]

OCA at 10:23, 11 August 2016

OCA — Thu, 11 Aug 2016 10:23:18 GMT

←Older revision		Revision as of 10:23, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor==		==Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor==
	<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [http://www.ebi.ac.uk/pdbsum/3w69 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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [http://pdbe.org/3w69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [http://www.ebi.ac.uk/pdbsum/3w69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3w69 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 3w69" style="background-color:#fffaf0;"></div>

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

OCA at 10:49, 4 January 2015

OCA — Sun, 04 Jan 2015 10:49:47 GMT

←Older revision		Revision as of 10:49, 4 January 2015
Line 2:		Line 2:
	<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3w69]] is a 2 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=3W69 OCA]. <br>	+	<table><tr><td colspan='2'>[[3w69]] is a 2 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=3W69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W69 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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 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~~><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class~~='~~plainlinks~~'~~>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [http://www.ebi.ac.uk/pdbsum/3w69 PDBsum]</span></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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [http://www.ebi.ac.uk/pdbsum/3w69 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 18:		Line 17:
	Synthesis and evaluation of novel orally active p53-MDM2 interaction inhibitors.,Miyazaki M, Naito H, Sugimoto Y, Yoshida K, Kawato H, Okayama T, Shimizu H, Miyazaki M, Kitagawa M, Seki T, Fukutake S, Shiose Y, Aonuma M, Soga T Bioorg Med Chem. 2013 Jul 15;21(14):4319-31. doi: 10.1016/j.bmc.2013.04.056. Epub, 2013 Apr 30. PMID:23685175<ref>PMID:23685175</ref>		Synthesis and evaluation of novel orally active p53-MDM2 interaction inhibitors.,Miyazaki M, Naito H, Sugimoto Y, Yoshida K, Kawato H, Okayama T, Shimizu H, Miyazaki M, Kitagawa M, Seki T, Fukutake S, Shiose Y, Aonuma M, Soga T Bioorg Med Chem. 2013 Jul 15;21(14):4319-31. doi: 10.1016/j.bmc.2013.04.056. Epub, 2013 Apr 30. PMID:23685175<ref>PMID:23685175</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, 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>
		+
		+	==See Also==
		+	*[[MDM2\|MDM2]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Katakura, S.]]	+	[[Category: Katakura, S]]
-	[[Category: Kawato, H.]]	+	[[Category: Kawato, H]]
-	[[Category: Miyazaki, M.]]	+	[[Category: Miyazaki, M]]
-	[[Category: Naito, H.]]	+	[[Category: Naito, H]]
-	[[Category: Okayama, T.]]	+	[[Category: Okayama, T]]
-	[[Category: Shimizu, H.]]	+	[[Category: Shimizu, H]]
-	[[Category: Soga, T.]]	+	[[Category: Soga, T]]
-	[[Category: Sugimoto, Y.]]	+	[[Category: Sugimoto, Y]]
	[[Category: Ligase-ligase inhibitor complex]]		[[Category: Ligase-ligase inhibitor complex]]
	[[Category: P53]]		[[Category: P53]]
	[[Category: Ubiquitin-protein ligase e3 mdm2]]		[[Category: Ubiquitin-protein ligase e3 mdm2]]

OCA at 09:36, 1 May 2014

OCA — Thu, 01 May 2014 09:36:04 GMT

←Older revision		Revision as of 09:36, 1 May 2014
Line 2:		Line 2:
	<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	[[3w69]] is a 2 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=3W69 OCA]. <br>	+	<table><tr><td colspan='2'>[[3w69]] is a 2 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=3W69 OCA]. <br>
-	<b>[[Ligand\|Ligands:]]</b> <scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
-	<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><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 HUMAN])</td></tr>
-	<b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [http://www.ebi.ac.uk/pdbsum/3w69 PDBsum]</span><br>	+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></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=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [http://www.ebi.ac.uk/pdbsum/3w69 PDBsum]</span></td></tr>
		+	<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.
	== 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 ==		== Publication Abstract from PubMed ==
	We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53.		We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53.
Line 16:		Line 19:

	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>		From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:10, 30 April 2014

OCA — Wed, 30 Apr 2014 10:10:34 GMT

←Older revision		Revision as of 10:10, 30 April 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	[[3w69]] is a 2 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=3W69 OCA]. <br>		[[3w69]] is a 2 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=3W69 OCA]. <br>
		+	<b>[[Ligand\|Ligands:]]</b> <scene name='pdbligand=LTZ:(5R,6S)-2-[((2S,5R)-2-{[(3R)-4-ACETYL-3-METHYLPIPERAZIN-1-YL]CARBONYL}-5-ETHYLPYRROLIDIN-1-YL)CARBONYL]-5,6-BIS(4-CHLOROPHENYL)-3-ISOPROPYL-6-METHYL-5,6-DIHYDROIMIDAZO[2,1-B][1,3]THIAZOLE'>LTZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
	<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>		<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
		+	<b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3w69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w69 RCSB], [http://www.ebi.ac.uk/pdbsum/3w69 PDBsum]</span><br>
	== 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.

OCA at 05:17, 30 April 2014

OCA — Wed, 30 Apr 2014 05:17:29 GMT

←Older revision		Revision as of 05:17, 30 April 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3w69\| PDB=3w69 \| SCENE= }}~~	+	==Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor==
-	===Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor===	+	<StructureSection load='3w69' size='340' side='right' caption='[[3w69]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23685175}}~~	+	== Structural highlights ==
-		+	[[3w69]] is a 2 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=3W69 OCA]. <br>
-	==Disease==	+	<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br>
		+	== 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>
		+	== Publication Abstract from PubMed ==
		+	We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53.

-	~~==About this Structure==~~	+	Synthesis and evaluation of novel orally active p53-MDM2 interaction inhibitors.,Miyazaki M, Naito H, Sugimoto Y, Yoshida K, Kawato H, Okayama T, Shimizu H, Miyazaki M, Kitagawa M, Seki T, Fukutake S, Shiose Y, Aonuma M, Soga T Bioorg Med Chem. 2013 Jul 15;21(14):4319-31. doi: 10.1016/j.bmc.2013.04.056. Epub, 2013 Apr 30. PMID:23685175<ref>PMID:23685175</ref>
-	~~[[3w69]] is a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.ac.~~il/oca-bin/ocashort?id=3W69 OCA]~~.	+

-	==~~Reference~~==	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:023685175</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	== References ==
-	[[Category: ~~Homo sapiens~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Katakura, S.]]		[[Category: Katakura, S.]]
	[[Category: Kawato, H.]]		[[Category: Kawato, H.]]

OCA at 15:53, 19 June 2013

OCA — Wed, 19 Jun 2013 15:53:21 GMT

←Older revision		Revision as of 15:53, 19 June 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_3w69\| PDB=3w69 \| SCENE= }}
		+	===Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor===
		+	{{ABSTRACT_PUBMED_23685175}}

-	~~The entry 3w69 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~~: ~~Shimizu, H~~.~~, Katakura, S~~., ~~Miyazaki, M~~.~~, Naito, H~~.~~, Sugimoto, Y~~.~~, Kawato, H~~.~~, Okayama, T~~.~~, Soga, T~~.	+	==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: Crystal~~ structure ~~of human mdm2~~ with ~~a dihydroimidazothiazole~~ inhibitor	+	==About this Structure==
		+	[[3w69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W69 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023685175</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Katakura, S.]]
		+	[[Category: Kawato, H.]]
		+	[[Category: Miyazaki, M.]]
		+	[[Category: Naito, H.]]
		+	[[Category: Okayama, T.]]
		+	[[Category: Shimizu, H.]]
		+	[[Category: Soga, T.]]
		+	[[Category: Sugimoto, Y.]]
		+	[[Category: Ligase-ligase inhibitor complex]]
		+	[[Category: P53]]
		+	[[Category: Ubiquitin-protein ligase e3 mdm2]]

OCA at 14:05, 27 February 2013

OCA — Wed, 27 Feb 2013 14:05:02 GMT

←Older revision		Revision as of 14:05, 27 February 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3w69 is ON HOLD	+	The entry 3w69 is ON HOLD until Paper Publication

-	Authors: Shimizu, H. , Katakura, S. , Miyazaki, M. , Naito, H. , Sugimoto, Y. , Kawato, H. , Okayama, T. , Soga, T.	+	Authors: Shimizu, H., Katakura, S., Miyazaki, M., Naito, H., Sugimoto, Y., Kawato, H., Okayama, T., Soga, T.

	Description: Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor		Description: Crystal structure of human mdm2 with a dihydroimidazothiazole inhibitor

OCA: Protected "3w69" [edit=sysop:move=sysop]

OCA — Wed, 20 Feb 2013 13:11:07 GMT

Protected "3w69" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:11, 20 February 2013