6v4e - Revision history

OCA at 13:12, 6 November 2024

2024-11-06T13:12:50Z

← Older revision		Revision as of 13:12, 6 November 2024
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	<StructureSection load='6v4e' size='340' side='right'caption='[[6v4e]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='6v4e' size='340' side='right'caption='[[6v4e]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[6v4e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4E FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4E FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.62Å</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]] 1.62Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6v4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4e OCA], [https://pdbe.org/6v4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4e RCSB], [https://www.ebi.ac.uk/pdbsum/6v4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4e 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=6v4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4e OCA], [https://pdbe.org/6v4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4e RCSB], [https://www.ebi.ac.uk/pdbsum/6v4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4e ProSAT]</span></td></tr>
	</table>		</table>
	~~== Function ==~~
	~~[https://www.uniprot.org/uniprot/MDM4_DANRE MDM4_DANRE] Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity).~~
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	p53 is a critical tumor-suppressor protein that guards the human genome against mutations by inducing cell-cycle arrest or apoptosis. Cancer cells subvert p53 by deletion, mutation, or overexpression of the negative regulators HDM2 and HDMX. For tumors that retain wild-type p53, its reactivation by pharmacologic targeting of HDM2 and/or HDMX represents a promising strategy, with a series of selective small-molecule HDM2 inhibitors and a dual HDM2/HDMX stapled-peptide inhibitor being evaluated in clinical trials. Because selective HDM2 targeting can cause hematologic toxicity, selective HDMX inhibitors could provide an alternative p53-reactivation strategy, but clinical candidates remain elusive. Here, we applied a mutation-scanning approach to uncover p53-based stapled peptides that are selective for HDMX. Crystal structures of stapled-peptide/HDMX complexes revealed a molecular mechanism for the observed specificity, which was validated by HDMX mutagenesis. Thus, we provide a blueprint for the development of HDMX-selective inhibitors to dissect and target the p53/HDMX interaction.

	Identification of a Structural Determinant for Selective Targeting of HDMX.,Ben-Nun Y, Seo HS, Harvey EP, Hauseman ZJ, Wales TE, Newman CE, Cathcart AM, Engen JR, Dhe-Paganon S, Walensky LD Structure. 2020 Jul 7;28(7):847-857.e5. doi: 10.1016/j.str.2020.04.011. Epub 2020, Apr 30. PMID:32359398<ref>PMID:32359398</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 6v4e" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[MDM4\|MDM4]]		*[[MDM4\|MDM4]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Danio rerio]]~~
	~~[[Category: Homo sapiens]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Dhe-Paganon S]]		[[Category: Dhe-Paganon S]]
	[[Category: Seo H-S]]		[[Category: Seo H-S]]

OCA at 08:03, 11 October 2023

2023-10-11T08:03:35Z

← Older revision		Revision as of 08:03, 11 October 2023
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	<StructureSection load='6v4e' size='340' side='right'caption='[[6v4e]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='6v4e' size='340' side='right'caption='[[6v4e]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6v4e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Brachidanio_rerio Brachidanio~~ rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[6v4e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4E FirstGlance]. <br>
	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non~~-~~Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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]] 1.62Å</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">mdm4, mdmx ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6v4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4e OCA], [https://pdbe.org/6v4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4e RCSB], [https://www.ebi.ac.uk/pdbsum/6v4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4e 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=6v4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4e OCA], [https://pdbe.org/6v4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4e RCSB], [https://www.ebi.ac.uk/pdbsum/6v4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/MDM4_DANRE MDM4_DANRE]] Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity).		[https://www.uniprot.org/uniprot/MDM4_DANRE MDM4_DANRE] Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Brachidanio~~ rerio]]		[[Category: Danio rerio]]
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Dhe-Paganon, S]]		[[Category: Dhe-Paganon S]]
	[[Category: Seo, H S]]		[[Category: Seo H-S]]
	~~[[Category: Apoptosis]]~~
	~~[[Category: P53 binding~~]]

OCA at 08:58, 5 May 2021

2021-05-05T08:58:29Z

← Older revision		Revision as of 08:58, 5 May 2021
Line 1:		Line 1:

	==Crystal Structure Analysis of Zebra Fish MDM==		==Crystal Structure Analysis of Zebra Fish MDM==
	<StructureSection load='6v4e' size='340' side='right'caption='[[6v4e]]' scene=''>		<StructureSection load='6v4e' size='340' side='right'caption='[[6v4e]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6V4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[6v4e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4E FirstGlance]. <br>
	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6v4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4e OCA], [~~http~~://pdbe.org/6v4e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6v4e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6v4e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4e ProSAT]</span></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">mdm4, mdmx ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=6v4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4e OCA], [https://pdbe.org/6v4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4e RCSB], [https://www.ebi.ac.uk/pdbsum/6v4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4e ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/MDM4_DANRE MDM4_DANRE]] Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity).
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			p53 is a critical tumor-suppressor protein that guards the human genome against mutations by inducing cell-cycle arrest or apoptosis. Cancer cells subvert p53 by deletion, mutation, or overexpression of the negative regulators HDM2 and HDMX. For tumors that retain wild-type p53, its reactivation by pharmacologic targeting of HDM2 and/or HDMX represents a promising strategy, with a series of selective small-molecule HDM2 inhibitors and a dual HDM2/HDMX stapled-peptide inhibitor being evaluated in clinical trials. Because selective HDM2 targeting can cause hematologic toxicity, selective HDMX inhibitors could provide an alternative p53-reactivation strategy, but clinical candidates remain elusive. Here, we applied a mutation-scanning approach to uncover p53-based stapled peptides that are selective for HDMX. Crystal structures of stapled-peptide/HDMX complexes revealed a molecular mechanism for the observed specificity, which was validated by HDMX mutagenesis. Thus, we provide a blueprint for the development of HDMX-selective inhibitors to dissect and target the p53/HDMX interaction.

			Identification of a Structural Determinant for Selective Targeting of HDMX.,Ben-Nun Y, Seo HS, Harvey EP, Hauseman ZJ, Wales TE, Newman CE, Cathcart AM, Engen JR, Dhe-Paganon S, Walensky LD Structure. 2020 Jul 7;28(7):847-857.e5. doi: 10.1016/j.str.2020.04.011. Epub 2020, Apr 30. PMID:32359398<ref>PMID:32359398</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 6v4e" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[MDM4\|MDM4]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Brachidanio rerio]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Dhe-Paganon S]]		[[Category: Dhe-Paganon, S]]
	[[Category: Seo H-S]]		[[Category: Seo, H S]]
			[[Category: Apoptosis]]
			[[Category: P53 binding]]

OCA at 05:47, 22 April 2020

2020-04-22T05:47:00Z

← Older revision		Revision as of 05:47, 22 April 2020
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 6v4e is ~~ON HOLD until Paper Publication~~		==Crystal Structure Analysis of Zebra Fish MDM==
			<StructureSection load='6v4e' size='340' side='right'caption='[[6v4e]]' scene=''>
	~~Authors~~: ~~Seo~~, H.-S., ~~Dhe~~-~~Paganon, S~~.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V4E FirstGlance]. <br>
	~~Description: Crystal Structure Analysis of Zebra Fish MDM~~		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4e OCA], [http://pdbe.org/6v4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v4e RCSB], [http://www.ebi.ac.uk/pdbsum/6v4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4e ProSAT]</span></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		</table>
	[[Category: Dhe-Paganon, S]]		__TOC__
	[[Category: Seo, H.-S]]		</StructureSection>
			[[Category: Large Structures]]
			[[Category: Dhe-Paganon S]]
			[[Category: Seo H-S]]

OCA at 13:44, 11 December 2019

2019-12-11T13:44:06Z

← Older revision		Revision as of 13:44, 11 December 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 6v4e is ON HOLD		The entry 6v4e is ON HOLD until Paper Publication

	Authors: Seo, H.-S., Dhe-Paganon, S.		Authors: Seo, H.-S., Dhe-Paganon, S.

	Description: Crystal Structure Analysis of ~~human MDMX~~		Description: Crystal Structure Analysis of Zebra Fish MDM
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Dhe-Paganon, S]]		[[Category: Dhe-Paganon, S]]
	[[Category: Seo, H.-S]]		[[Category: Seo, H.-S]]

OCA: Protected "6v4e" [edit=sysop:move=sysop]

2019-12-04T06:42:46Z

Protected "6v4e" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:42, 4 December 2019
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6v4e is ON HOLD Authors: Seo, H.-S., Dhe-Paganon, S. Description: Crystal Structure Analysis of human MDMX Category: Unreleased Structures [[Ca...

2019-12-04T06:42:45Z

New page: '''Unreleased structure''' The entry 6v4e is ON HOLD Authors: Seo, H.-S., Dhe-Paganon, S. Description: Crystal Structure Analysis of human MDMX Category: Unreleased Structures [[Ca...

New page

'''Unreleased structure'''

The entry 6v4e is ON HOLD

Authors: Seo, H.-S., Dhe-Paganon, S.

Description: Crystal Structure Analysis of human MDMX
[[Category: Unreleased Structures]]
[[Category: Dhe-Paganon, S]]
[[Category: Seo, H.-S]]