6zrd - Revision history

OCA at 11:56, 1 February 2024

OCA — Thu, 01 Feb 2024 11:56:59 GMT

←Older revision		Revision as of 11:56, 1 February 2024
Line 1:		Line 1:

-	====	+	==STRUCTURE OF THE HUMAN RBAP48 in complex with a macrocyclic peptide cyclized via a xylene linker attached to two cysteines==
-	<StructureSection load='6zrd' size='340' side='right'caption='[[6zrd]]' scene=''>	+	<StructureSection load='6zrd' size='340' side='right'caption='[[6zrd]], [[Resolution\|resolution]] 2.50Å' 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'>[[6zrd]] is a 4 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=6ZRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZRD 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=6zrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zrd OCA], [https://pdbe.org/6zrd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zrd RCSB], [https://www.ebi.ac.uk/pdbsum/6zrd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zrd 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]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SEZ:1,3,5-trimethylbenzene'>SEZ</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=6zrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zrd OCA], [https://pdbe.org/6zrd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zrd RCSB], [https://www.ebi.ac.uk/pdbsum/6zrd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zrd ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RBBP4_HUMAN RBBP4_HUMAN] Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex.<ref>PMID:10866654</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The scaffolding protein RbAp48 is part of several epigenetic regulation complexes and is overexpressed in a variety of cancers. In order to develop tool compounds for the study of RbAp48 function, we have developed peptide inhibitors targeting the protein-protein interaction interface between RbAp48 and the scaffold protein MTA1. Based on a MTA1-derived linear peptide with low micromolar affinity and informed by crystallographic analysis, a bicyclic peptide was developed that inhibits the RbAp48/MTA1 interaction with a very low nanomolar KD value of 8.56 nM, and which showed appreciable stability against cellular proteases. Design included exchange of a polar amide cyclization strategy to hydrophobic aromatic linkers enabling mono- and bicyclization by means of cysteine alkylation, which improved affinity by direct interaction of the linkers with a hydrophobic residue on RbAp48. Our results demonstrate that stepwise evolution of a structure-based design is a suitable strategy for inhibitor development targeting PPIs.
		+
		+	Structure based design of bicyclic peptide inhibitors of RbAp48.,Waldmann H, 't Hart P, Hommen P, Noisier A, Krzyzanowski A, Schuler D, Porfetye AT, Akbarzadeh M, Vetter IR, Adihou H Angew Chem Int Ed Engl. 2020 Oct 6. doi: 10.1002/anie.202009749. PMID:33022847<ref>PMID:33022847</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zrd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Retinoblastoma-binding protein 3D structures\|Retinoblastoma-binding protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Porfetye AT]]
		+	[[Category: Vetter IR]]

OCA at 08:02, 27 January 2021

OCA — Wed, 27 Jan 2021 08:02:04 GMT

←Older revision		Revision as of 08:02, 27 January 2021
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	<StructureSection load='6zrd' size='340' side='right'caption='[[6zrd]]' scene=''>		<StructureSection load='6zrd' size='340' side='right'caption='[[6zrd]]' 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 [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<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>
-	</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=6zrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zrd OCA], [~~http~~://pdbe.org/6zrd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6zrd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6zrd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6zrd ProSAT]</span></td></tr>	+	</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=6zrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zrd OCA], [https://pdbe.org/6zrd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zrd RCSB], [https://www.ebi.ac.uk/pdbsum/6zrd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zrd ProSAT]</span></td></tr>
	</table>		</table>
	__TOC__		__TOC__

OCA at 07:48, 2 December 2020

OCA — Wed, 02 Dec 2020 07:48:54 GMT

←Older revision		Revision as of 07:48, 2 December 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6zrd ~~is ON HOLD~~	+	====
-		+	<StructureSection load='6zrd' size='340' side='right'caption='[[6zrd]]' 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 [http://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'>[http://proteopedia.org/fgij/fg.htm?mol=6zrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zrd OCA], [http://pdbe.org/6zrd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zrd RCSB], [http://www.ebi.ac.uk/pdbsum/6zrd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zrd ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

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

OCA — Wed, 22 Jul 2020 08:16:15 GMT

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

←Older revision

Revision as of 08:16, 22 July 2020

OCA: New page: '''Unreleased structure''' The entry 6zrd is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 22 Jul 2020 08:16:14 GMT

New page: '''Unreleased structure''' The entry 6zrd is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6zrd is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]