OCA at 12:41, 1 February 2024

2024-02-01T12:41:57Z

←Older revision		Revision as of 12:41, 1 February 2024
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-	====	+	==14-3-3 sigma with RelA/p65 binding site pS45 and covalently bound TCF521-125==
-	<StructureSection load='7nz6' size='340' side='right'caption='[[7nz6]]' scene=''>	+	<StructureSection load='7nz6' size='340' side='right'caption='[[7nz6]], [[Resolution\|resolution]] 1.40Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7nz6]] 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=7NZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NZ6 FirstGlance]. <br>
-	</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=7nz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nz6 OCA], [https://pdbe.org/7nz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nz6 RCSB], [https://www.ebi.ac.uk/pdbsum/7nz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nz6 ProSAT]</span></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]] 1.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=UWH:4-[4-(2-methoxyethyl)piperazin-1-yl]sulfonylbenzaldehyde'>UWH</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=7nz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nz6 OCA], [https://pdbe.org/7nz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nz6 RCSB], [https://www.ebi.ac.uk/pdbsum/7nz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nz6 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/TF65_HUMAN TF65_HUMAN] NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1.<ref>PMID:10928981</ref> <ref>PMID:12748188</ref> <ref>PMID:17000776</ref> <ref>PMID:17620405</ref> <ref>PMID:19058135</ref> <ref>PMID:20547752</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein-protein modulation has emerged as a proven approach to drug discovery. While significant progress has been gained in developing protein-protein interaction (PPI) inhibitors, the orthogonal approach of PPI stabilization lacks established methodologies for drug design. Here, we report the systematic ''bottom-up'' development of a reversible covalent PPI stabilizer. An imine bond was employed to anchor the stabilizer at the interface of the 14-3-3/p65 complex, leading to a molecular glue that elicited an 81-fold increase in complex stabilization. Utilizing protein crystallography and biophysical assays, we deconvoluted how chemical properties of a stabilizer translate to structural changes in the ternary 14-3-3/p65/molecular glue complex. Furthermore, we explore how this leads to high cooperativity and increased stability of the complex.
		+
		+	An Exploration of Chemical Properties Required for Cooperative Stabilization of the 14-3-3 Interaction with NF-kappaB-Utilizing a Reversible Covalent Tethering Approach.,Wolter M, Valenti D, Cossar PJ, Hristeva S, Levy LM, Genski T, Hoffmann T, Brunsveld L, Tzalis D, Ottmann C J Med Chem. 2021 Jun 24;64(12):8423-8436. doi: 10.1021/acs.jmedchem.1c00401. Epub , 2021 Jun 2. PMID:34076416<ref>PMID:34076416</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7nz6" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[14-3-3 protein 3D structures\|14-3-3 protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Ottmann C]]
		+	[[Category: Wolter M]]

OCA at 12:15, 9 June 2021

2021-06-09T12:15:11Z

←Older revision		Revision as of 12:15, 9 June 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7nz6 ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7nz6' size='340' side='right'caption='[[7nz6]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7nz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nz6 OCA], [https://pdbe.org/7nz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nz6 RCSB], [https://www.ebi.ac.uk/pdbsum/7nz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nz6 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 04:46, 7 April 2021

2021-04-07T04:46:58Z

←Older revision		Revision as of 04:46, 7 April 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7nz6 is ON HOLD	+	The entry 7nz6 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7nz6" [edit=sysop:move=sysop]

2021-03-31T09:33:57Z

Protected "7nz6" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:33, 31 March 2021

OCA: New page: '''Unreleased structure''' The entry 7nz6 is ON HOLD Authors: Description: Category: Unreleased Structures

2021-03-31T09:33:56Z

New page: '''Unreleased structure''' The entry 7nz6 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7nz6 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7nz6 - Revision history

OCA at 12:41, 1 February 2024

OCA at 12:15, 9 June 2021

OCA at 04:46, 7 April 2021

OCA: Protected "7nz6" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7nz6 is ON HOLD Authors: Description: Category: Unreleased Structures