6qhm - Revision history

OCA at 12:01, 24 January 2024

OCA — Wed, 24 Jan 2024 12:01:16 GMT

←Older revision		Revision as of 12:01, 24 January 2024
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	<StructureSection load='6qhm' size='340' side='right'caption='[[6qhm]], [[Resolution\|resolution]] 1.25Å' scene=''>		<StructureSection load='6qhm' size='340' side='right'caption='[[6qhm]], [[Resolution\|resolution]] 1.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qhm]] 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=6QHM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6QHM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qhm]] 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=6QHM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QHM FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=CSO:S~~-~~HYDROXYCYSTEINE'>CSO</scene>~~, ~~<scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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]] 1.25Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~SFN, HME1 ([http~~:/~~/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=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=6qhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qhm OCA], [~~http~~://pdbe.org/6qhm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qhm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qhm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qhm 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=6qhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qhm OCA], [https://pdbe.org/6qhm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qhm RCSB], [https://www.ebi.ac.uk/pdbsum/6qhm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qhm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.	+	[https://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Natural compounds are an important class of potent drug molecules including some retrospectively found to act as stabilizers of protein-protein interactions (PPIs). However, the design of synthetic PPI stabilizers remains an understudied approach. To date, there are limited examples where cooperativity has been utilized to guide the optimization of a PPI stabilizer. The 14-3-3 scaffold proteins provide an excellent platform to explore PPI stabilization because these proteins mediate several hundred PPIs, and a class of natural compounds, the fusicoccanes, are known to stabilize a subset of 14-3-3 protein interactions. 14-3-3 has been reported to negatively regulate the p65 subunit of the NF-kappaB transcription factor, which qualifies this protein complex as a potential target for drug discovery to control cell proliferation. Here, we report the high-resolution crystal structures of two 14-3-3 binding motifs of p65 in complex with 14-3-3. A semisynthetic natural product derivative, DP-005, binds to an interface pocket of the p65/14-3-3 complex and concomitantly stabilizes it. Cooperativity analyses of this interaction, and other disease relevant 14-3-3-PPIs, demonstrated selectivity of DP-005 for the p65/14-3-3 complex. The adaptation of a cooperative binding model provided a general approach to characterize stabilization and to assay for selectivity of PPI stabilizers.
		+
		+	Selectivity via Cooperativity: Preferential Stabilization of the p65/14-3-3 Interaction with Semisynthetic Natural Products.,Wolter M, de Vink P, Neves JF, Srdanovic S, Higuchi Y, Kato N, Wilson A, Landrieu I, Brunsveld L, Ottmann C J Am Chem Soc. 2020 Jun 23. doi: 10.1021/jacs.0c02151. PMID:32501683<ref>PMID:32501683</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qhm" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]		*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ottmann, C]]	+	[[Category: Ottmann C]]
-	[[Category: Wolter, M]]	+	[[Category: Wolter M]]
-	~~[[Category: 14-3-3]]~~	+
-	~~[[Category: 14-3-3 sigma]]~~	+
-	~~[[Category: P65]]~~	+
-	~~[[Category: Peptide binding protein]]~~	+
-	~~[[Category: Rela~~]]	+

OCA at 07:01, 25 June 2020

OCA — Thu, 25 Jun 2020 07:01:29 GMT

←Older revision		Revision as of 07:01, 25 June 2020
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	==14-3-3 sigma with RelA/p65 binding site pS281==		==14-3-3 sigma with RelA/p65 binding site pS281==
-	<StructureSection load='6qhm' size='340' side='right'caption='[[6qhm]]' scene=''>	+	<StructureSection load='6qhm' size='340' side='right'caption='[[6qhm]], [[Resolution\|resolution]] 1.25Å' 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=6QHM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QHM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qhm]] 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=6QHM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QHM 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=6qhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qhm OCA], [http://pdbe.org/6qhm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qhm RCSB], [http://www.ebi.ac.uk/pdbsum/6qhm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qhm 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=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SFN, HME1 ([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://proteopedia.org/fgij/fg.htm?mol=6qhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qhm OCA], [http://pdbe.org/6qhm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qhm RCSB], [http://www.ebi.ac.uk/pdbsum/6qhm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qhm ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
		+
		+	==See Also==
		+	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ottmann C]]	+	[[Category: Ottmann, C]]
-	[[Category: Wolter M]]	+	[[Category: Wolter, M]]
		+	[[Category: 14-3-3]]
		+	[[Category: 14-3-3 sigma]]
		+	[[Category: P65]]
		+	[[Category: Peptide binding protein]]
		+	[[Category: Rela]]

OCA at 05:27, 13 May 2020

OCA — Wed, 13 May 2020 05:27:47 GMT

←Older revision		Revision as of 05:27, 13 May 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6qhm is ON HOLD until Paper Publication~~	+	==14-3-3 sigma with RelA/p65 binding site pS281==
-		+	<StructureSection load='6qhm' size='340' side='right'caption='[[6qhm]]' scene=''>
-	~~Authors: Wolter, M., Ottmann, C.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QHM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QHM FirstGlance]. <br>
-	~~Description:~~ 14-3-3 sigma with RelA/p65 binding site pS281	+	</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=6qhm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qhm OCA], [http://pdbe.org/6qhm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qhm RCSB], [http://www.ebi.ac.uk/pdbsum/6qhm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qhm ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Ottmann, C]]	+	__TOC__
-	[[Category: Wolter, M]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ottmann C]]
		+	[[Category: Wolter M]]

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

OCA — Wed, 30 Jan 2019 06:58:36 GMT

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

←Older revision

Revision as of 06:58, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6qhm is ON HOLD until Paper Publication Authors: Wolter, M., Ottmann, C. Description: 14-3-3 sigma with RelA/p65 binding site pS281 [[Category: Unr...

OCA — Wed, 30 Jan 2019 06:58:35 GMT

New page: '''Unreleased structure''' The entry 6qhm is ON HOLD until Paper Publication Authors: Wolter, M., Ottmann, C. Description: 14-3-3 sigma with RelA/p65 binding site pS281 [[Category: Unr...

New page

'''Unreleased structure'''

The entry 6qhm is ON HOLD until Paper Publication

Authors: Wolter, M., Ottmann, C.

Description: 14-3-3 sigma with RelA/p65 binding site pS281
[[Category: Unreleased Structures]]
[[Category: Ottmann, C]]
[[Category: Wolter, M]]