6q9u - Revision history

OCA at 11:56, 24 January 2024

OCA — Wed, 24 Jan 2024 11:56:23 GMT

←Older revision		Revision as of 11:56, 24 January 2024
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	<StructureSection load='6q9u' size='340' side='right'caption='[[6q9u]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='6q9u' size='340' side='right'caption='[[6q9u]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6q9u]] is a 1 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=6Q9U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6Q9U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6q9u]] is a 1 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=6Q9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q9U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HRE:4-[(4~{S})-5-(5-chloranyl-2-oxidanylidene-1~{H}-pyridin-3-yl)-2-[2-(dimethylamino)-4-methoxy-pyrimidin-5-yl]-6-oxidanylidene-3-propan-2-yl-4~{H}-pyrrolo[3,4-c]pyrazol-4-yl]benzenecarbonitrile'>HRE</scene>, <scene name='pdbligand=O4B:1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE'>O4B</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]] 2.4Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6q96\|6q96]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HRE:4-[(4~{S})-5-(5-chloranyl-2-oxidanylidene-1~{H}-pyridin-3-yl)-2-[2-(dimethylamino)-4-methoxy-pyrimidin-5-yl]-6-oxidanylidene-3-propan-2-yl-4~{H}-pyrrolo[3,4-c]pyrazol-4-yl]benzenecarbonitrile'>HRE</scene>, <scene name='pdbligand=O4B:1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE'>O4B</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM4, MDMX ([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=6q9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q9u OCA], [https://pdbe.org/6q9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q9u RCSB], [https://www.ebi.ac.uk/pdbsum/6q9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q9u 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=6q9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q9u OCA], [~~http~~://pdbe.org/6q9u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6q9u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6q9u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6q9u ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MDM4_HUMAN MDM4_HUMAN]] Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.<ref>PMID:16163388</ref> <ref>PMID:16511572</ref>	+	[https://www.uniprot.org/uniprot/MDM4_HUMAN MDM4_HUMAN] Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.<ref>PMID:16163388</ref> <ref>PMID:16511572</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6q9u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6q9u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[MDM4\|MDM4]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kallen, J]]	+	[[Category: Kallen J]]
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Hdmx]]~~	+
-	~~[[Category: Mdm4~~]]	+

OCA at 07:38, 21 May 2019

OCA — Tue, 21 May 2019 07:38:06 GMT

←Older revision		Revision as of 07:38, 21 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6q9u is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==HDMX (14-111; C17S) COMPLEXED WITH COMPOUND 12 AT 2.4A; Structural states of Hdm2 and HdmX: X-ray elucidation of adaptations and binding interactions for different chemical compound classes==
		+	<StructureSection load='6q9u' size='340' side='right'caption='[[6q9u]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6q9u]] is a 1 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=6Q9U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q9U FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HRE:4-[(4~{S})-5-(5-chloranyl-2-oxidanylidene-1~{H}-pyridin-3-yl)-2-[2-(dimethylamino)-4-methoxy-pyrimidin-5-yl]-6-oxidanylidene-3-propan-2-yl-4~{H}-pyrrolo[3,4-c]pyrazol-4-yl]benzenecarbonitrile'>HRE</scene>, <scene name='pdbligand=O4B:1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE'>O4B</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6q96\|6q96]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MDM4, MDMX ([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=6q9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q9u OCA], [http://pdbe.org/6q9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q9u RCSB], [http://www.ebi.ac.uk/pdbsum/6q9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q9u ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MDM4_HUMAN MDM4_HUMAN]] Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.<ref>PMID:16163388</ref> <ref>PMID:16511572</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hdm2 (human MDM2) counteracts p53 function by direct binding to p53 and by ubiquitin-dependent p53 protein degradation. Activation of p53 by inhibitors of the p53-Hdm2 interaction is being pursued as a therapeutic strategy in p53 wild-type cancers. In addition, HdmX (human MDMX, human MDM4) was also identified as an important therapeutic target to efficiently reactivate p53, and it is likely that dual inhibition of Hdm2 and HdmX is beneficial. Here, we report four new X-ray structures for Hdm2 and five new X-ray structures for HdmX complexes, involving different classes of synthetic compounds. We also reveal the key additive 18-crown-ether, which we have discovered to enable HdmX crystallization and show its stabilization of various Lys-residues. In addition, we report the previously unpublished details of X-ray structure determinations for eight further Hdm2 complexes, including the clinical trial compounds NVP-CGM097 and NVP-HDM201. An analysis of all compound binding modes reveals new and deepened insights into the possible adaptations and structural states of Hdm2 (e.g. flip of F55; flip of Y67; reorientation of H96) and HdmX (e.g. flip of H55; dimer induction), enabling key binding interactions for different compound classes. In order to make comparisons easier, we have used the same numbering for Hdm2 and HdmX. Taken together, these structural insights should prove useful for the design and optimization of further selective and/or dual Hdm2/HdmX inhibitors.

-	~~Authors~~: Kallen, J.	+	Structural states of Hdm2 and HdmX: X-ray elucidation of adaptations and binding interactions for different chemical compound classes.,Kallen J, Izaac A, Chau S, Wirth E, Schoepfer J, Mah R, Schlapbach A, Stutz S, Vaupel A, Guagnano V, Masuya K, Stachyra TM, Salem B, Chene P, Gessier F, Holzer P, Furet P ChemMedChem. 2019 May 8. doi: 10.1002/cmdc.201900201. PMID:31066983<ref>PMID:31066983</ref>

-	~~Description: HDMX (14-111~~; ~~C17S) COMPLEXED WITH COMPOUND 12 AT 2.4A~~; ~~Structural states~~ of ~~Hdm2 and HdmX: X-ray elucidation~~ of ~~adaptations and binding interactions for different chemical compound classes~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6q9u" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Kallen, J]]		[[Category: Kallen, J]]
		+	[[Category: Apoptosis]]
		+	[[Category: Hdmx]]
		+	[[Category: Mdm4]]

OCA: Protected "6q9u" [edit=sysop:move=sysop]

OCA — Wed, 26 Dec 2018 07:01:20 GMT

Protected "6q9u" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:01, 26 December 2018

OCA: New page: '''Unreleased structure''' The entry 6q9u is ON HOLD until Paper Publication Authors: Kallen, J. Description: HDMX (14-111; C17S) COMPLEXED WITH COMPOUND 12 AT 2.4A; Structural states ...

OCA — Wed, 26 Dec 2018 07:01:19 GMT

New page: '''Unreleased structure''' The entry 6q9u is ON HOLD until Paper Publication Authors: Kallen, J. Description: HDMX (14-111; C17S) COMPLEXED WITH COMPOUND 12 AT 2.4A; Structural states ...

New page

'''Unreleased structure'''

The entry 6q9u is ON HOLD until Paper Publication

Authors: Kallen, J.

Description: HDMX (14-111; C17S) COMPLEXED WITH COMPOUND 12 AT 2.4A; Structural states of Hdm2 and HdmX: X-ray elucidation of adaptations and binding interactions for different chemical compound classes
[[Category: Unreleased Structures]]
[[Category: Kallen, J]]