4j7e - Revision history

OCA at 12:01, 1 March 2024

OCA — Fri, 01 Mar 2024 12:01:54 GMT

←Older revision		Revision as of 12:01, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4j7e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J7E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4j7e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J7E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I29:[(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2,4,5-TRIMETHYL-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]{4-[3-(METHYLSULFONYL)PROPYL]PIPERAZIN-1-YL}METHANONE'>I29</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]] 1.63Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=I29:[(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2,4,5-TRIMETHYL-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]{4-[3-(METHYLSULFONYL)PROPYL]PIPERAZIN-1-YL}METHANONE'>I29</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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [https://pdbe.org/4j7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [https://www.ebi.ac.uk/pdbsum/4j7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j7e 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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [https://pdbe.org/4j7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [https://www.ebi.ac.uk/pdbsum/4j7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j7e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).		[https://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Protein-protein interaction (PPI) systems represent a rich potential source of targets for drug discovery, but historically have proven to be difficult, particularly in the lead identification stage. Application of the fragment-based approach may help toward success with this target class. To provide an example toward understanding the potential issues associated with such an application, we have deconstructed one of the best established protein-protein inhibitors, the Nutlin series that inhibits the interaction between MDM2 and p53, into fragments, and surveyed the resulting binding properties using heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR), surface plasmon resonance (SPR), and X-ray crystallography. We report the relative contributions toward binding affinity for each of the key substituents of the Nutlin molecule and show that this series could hypothetically have been discovered via a fragment approach. We find that the smallest fragment of Nutlin that retains binding accesses two subpockets of MDM2 and has a molecular weight at the high end of the range that normally defines fragments.
-
-	Deconstruction of a nutlin: dissecting the binding determinants of a potent protein-protein interaction inhibitor.,Fry DC, Wartchow C, Graves B, Janson C, Lukacs C, Kammlott U, Belunis C, Palme S, Klein C, Vu B ACS Med Chem Lett. 2013 May 24;4(7):660-5. doi: 10.1021/ml400062c. eCollection, 2013 Jul 11. PMID:24900726<ref>PMID:24900726</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4j7e" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[MDM2 3D structures\|MDM2 3D structures]]		*[[MDM2 3D structures\|MDM2 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 10:56, 24 November 2022

OCA — Thu, 24 Nov 2022 10:56:56 GMT

←Older revision		Revision as of 10:56, 24 November 2022
Line 1:		Line 1:

	==The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529==		==The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529==
-	<StructureSection load='4j7e' size='340' side='right' caption='[[4j7e]], [[Resolution\|resolution]] 1.63Å' scene=''>	+	<StructureSection load='4j7e' size='340' side='right'caption='[[4j7e]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4j7e]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~African_clawed_frog African clawed frog~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4J7E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4j7e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J7E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I29:[(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2,4,5-TRIMETHYL-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]{4-[3-(METHYLSULFONYL)PROPYL]PIPERAZIN-1-YL}METHANONE'>I29</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=I29:[(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2,4,5-TRIMETHYL-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]{4-[3-(METHYLSULFONYL)PROPYL]PIPERAZIN-1-YL}METHANONE'>I29</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4j74\|4j74]], [[4j7d\|4j7d]], [[4ipf\|4ipf]], [[4j3e\|4j3e]]</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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [https://pdbe.org/4j7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [https://www.ebi.ac.uk/pdbsum/4j7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j7e ProSAT]</span></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=8355 African clawed frog])~~</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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [~~http~~://pdbe.org/4j7e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4j7e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4j7e ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).	+	[https://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
-	*[[MDM2\|MDM2]]	+	*[[MDM2 3D structures\|MDM2 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~African clawed frog~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Graves, B~~]]	+	[[Category: Xenopus laevis]]
-	[[Category: ~~Janson, C~~]]	+	[[Category: Graves B]]
-	[[Category: ~~Lukacs,~~ C]]	+	[[Category: Janson C]]
-	[[Category: ~~E3 ubiquitin ligase]]~~	+	[[Category: Lukacs C]]
-	~~[[Category: Imidazoline]]~~	+
-	~~[[Category: Ligase-antagonist complex]]~~	+
-	~~[[Category: Mdm2]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: P53]]~~	+
-	~~[[Category: Protein-protein interaction~~]]	+

OCA at 20:37, 4 August 2016

OCA — Thu, 04 Aug 2016 20:37:22 GMT

←Older revision		Revision as of 20:37, 4 August 2016
Line 1:		Line 1:
		+
	==The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529==		==The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529==
	<StructureSection load='4j7e' size='340' side='right' caption='[[4j7e]], [[Resolution\|resolution]] 1.63Å' scene=''>		<StructureSection load='4j7e' size='340' side='right' caption='[[4j7e]], [[Resolution\|resolution]] 1.63Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4j74\|4j74]], [[4j7d\|4j7d]], [[4ipf\|4ipf]], [[4j3e\|4j3e]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4j74\|4j74]], [[4j7d\|4j7d]], [[4ipf\|4ipf]], [[4j3e\|4j3e]]</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=8355 African clawed frog])</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=8355 African clawed frog])</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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [http://www.ebi.ac.uk/pdbsum/4j7e 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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [http://pdbe.org/4j7e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [http://www.ebi.ac.uk/pdbsum/4j7e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j7e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	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 4j7e" style="background-color:#fffaf0;"></div>

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

OCA at 12:57, 25 December 2014

OCA — Thu, 25 Dec 2014 12:57:00 GMT

←Older revision		Revision as of 12:57, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4j7e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J7E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4j7e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J7E FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I29:[(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2,4,5-TRIMETHYL-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]{4-[3-(METHYLSULFONYL)PROPYL]PIPERAZIN-1-YL}METHANONE'>I29</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=I29:[(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2,4,5-TRIMETHYL-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]{4-[3-(METHYLSULFONYL)PROPYL]PIPERAZIN-1-YL}METHANONE'>I29</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4j74\|4j74]], [[4j7d\|4j7d]], [[4ipf\|4ipf]], [[4j3e\|4j3e]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4j74\|4j74]], [[4j7d\|4j7d]], [[4ipf\|4ipf]], [[4j3e\|4j3e]]</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=8355 African clawed frog])</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=8355 African clawed frog])</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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [http://www.ebi.ac.uk/pdbsum/4j7e 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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [http://www.ebi.ac.uk/pdbsum/4j7e PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: African clawed frog]]		[[Category: African clawed frog]]
-	[[Category: Graves, B.]]	+	[[Category: Graves, B]]
-	[[Category: Janson, C.]]	+	[[Category: Janson, C]]
-	[[Category: Lukacs, C.]]	+	[[Category: Lukacs, C]]
	[[Category: E3 ubiquitin ligase]]		[[Category: E3 ubiquitin ligase]]
	[[Category: Imidazoline]]		[[Category: Imidazoline]]

OCA at 06:27, 24 September 2014

OCA — Wed, 24 Sep 2014 06:27:30 GMT

←Older revision		Revision as of 06:27, 24 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4j7e\| PDB=4j7e \| SCENE= }}~~	+	==The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529==
-	===The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529===	+	<StructureSection load='4j7e' size='340' side='right' caption='[[4j7e]], [[Resolution\|resolution]] 1.63Å' scene=''>
-	{~~{ABSTRACT_PUBMED_14704432}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4j7e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J7E FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I29:[(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2,4,5-TRIMETHYL-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]{4-[3-(METHYLSULFONYL)PROPYL]PIPERAZIN-1-YL}METHANONE'>I29</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4j74\|4j74]], [[4j7d\|4j7d]], [[4ipf\|4ipf]], [[4j3e\|4j3e]]</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=8355 African clawed frog])</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=4j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j7e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j7e RCSB], [http://www.ebi.ac.uk/pdbsum/4j7e PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein-protein interaction (PPI) systems represent a rich potential source of targets for drug discovery, but historically have proven to be difficult, particularly in the lead identification stage. Application of the fragment-based approach may help toward success with this target class. To provide an example toward understanding the potential issues associated with such an application, we have deconstructed one of the best established protein-protein inhibitors, the Nutlin series that inhibits the interaction between MDM2 and p53, into fragments, and surveyed the resulting binding properties using heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR), surface plasmon resonance (SPR), and X-ray crystallography. We report the relative contributions toward binding affinity for each of the key substituents of the Nutlin molecule and show that this series could hypothetically have been discovered via a fragment approach. We find that the smallest fragment of Nutlin that retains binding accesses two subpockets of MDM2 and has a molecular weight at the high end of the range that normally defines fragments.

-	~~==Function==~~	+	Deconstruction of a nutlin: dissecting the binding determinants of a potent protein-protein interaction inhibitor.,Fry DC, Wartchow C, Graves B, Janson C, Lukacs C, Kammlott U, Belunis C, Palme S, Klein C, Vu B ACS Med Chem Lett. 2013 May 24;4(7):660-5. doi: 10.1021/ml400062c. eCollection, 2013 Jul 11. PMID:24900726<ref>PMID:24900726</ref>
-	~~[[http~~:~~//www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA]] E3 ubiquitin~~-protein ~~ligase that mediates ubiquitination of p53/TP53~~, ~~leading to its degration by the proteasome~~ (~~By similarity~~).	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4j7e]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Xenopus_laevis Xenopus laevis]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:014704432</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[MDM2\|MDM2]]
-	[[Category: ~~Xenopus laevis~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: African clawed frog]]
	[[Category: Graves, B.]]		[[Category: Graves, B.]]
	[[Category: Janson, C.]]		[[Category: Janson, C.]]

OCA at 20:51, 7 August 2013

OCA — Wed, 07 Aug 2013 20:51:01 GMT

←Older revision		Revision as of 20:51, 7 August 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4j7e\| PDB=4j7e \| SCENE= }}
		+	===The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529===
		+	{{ABSTRACT_PUBMED_14704432}}

-	~~The entry 4j7e is ON HOLD until Paper Publication~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).

-	~~Authors~~: ~~Janson, C~~.~~, Lukacs, C~~.~~, Graves, B~~.	+	==About this Structure==
		+	[[4j7e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J7E OCA].

-	~~Description~~: ~~The 1.63A crystal structure of humanized~~ Xenopus ~~MDM2 with a nutlin fragment~~, ~~RO5524529~~	+	==Reference==
		+	<ref group="xtra">PMID:014704432</ref><references group="xtra"/><references/>
		+	[[Category: Xenopus laevis]]
		+	[[Category: Graves, B.]]
		+	[[Category: Janson, C.]]
		+	[[Category: Lukacs, C.]]
		+	[[Category: E3 ubiquitin ligase]]
		+	[[Category: Imidazoline]]
		+	[[Category: Ligase-antagonist complex]]
		+	[[Category: Mdm2]]
		+	[[Category: Nucleus]]
		+	[[Category: P53]]
		+	[[Category: Protein-protein interaction]]

OCA at 00:50, 4 April 2013

OCA — Thu, 04 Apr 2013 00:50:41 GMT

←Older revision		Revision as of 00:50, 4 April 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4j7e is ON HOLD	+	The entry 4j7e is ON HOLD until Paper Publication

	Authors: Janson, C., Lukacs, C., Graves, B.		Authors: Janson, C., Lukacs, C., Graves, B.

	Description: The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529		Description: The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529

OCA at 16:16, 20 March 2013

OCA — Wed, 20 Mar 2013 16:16:38 GMT

←Older revision		Revision as of 16:16, 20 March 2013
Line 3:		Line 3:
	The entry 4j7e is ON HOLD		The entry 4j7e is ON HOLD

-	Authors: ~~JANSON~~, C., ~~LUKACS~~, C., ~~GRAVES~~, B.	+	Authors: Janson, C., Lukacs, C., Graves, B.

-	Description: ~~THE~~ 1.63A ~~CRYSTAL STRUCTURE OF HUMANIZED XENOPUS~~ MDM2 ~~WITH A NUTLIN FRAGMENT~~, RO5524529	+	Description: The 1.63A crystal structure of humanized Xenopus MDM2 with a nutlin fragment, RO5524529

OCA: Protected "4j7e" [edit=sysop:move=sysop]

OCA — Wed, 20 Feb 2013 13:33:04 GMT

Protected "4j7e" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:33, 20 February 2013

OCA: New page: '''Unreleased structure''' The entry 4j7e is ON HOLD Authors: JANSON, C., LUKACS, C., GRAVES, B. Description: THE 1.63A CRYSTAL STRUCTURE OF HUMANIZED XENOPUS MDM2 WITH A NUTLIN FRAGME...

OCA — Wed, 20 Feb 2013 13:33:03 GMT

New page: '''Unreleased structure''' The entry 4j7e is ON HOLD Authors: JANSON, C., LUKACS, C., GRAVES, B. Description: THE 1.63A CRYSTAL STRUCTURE OF HUMANIZED XENOPUS MDM2 WITH A NUTLIN FRAGME...

New page

'''Unreleased structure'''

The entry 4j7e is ON HOLD

Authors: JANSON, C., LUKACS, C., GRAVES, B.

Description: THE 1.63A CRYSTAL STRUCTURE OF HUMANIZED XENOPUS MDM2 WITH A NUTLIN FRAGMENT, RO5524529