5xf3: Difference between revisions
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==Nucleosome core particle with an adduct of a binuclear RAPTA (Ru-arene-phosphaadamantane) compound having a 1,2-diphenylethylenediamine linker (R,R-configuration)== | |||
<StructureSection load='5xf3' size='340' side='right'caption='[[5xf3]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5xf3]] is a 10 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=5XF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XF3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RRK:(1R,2R)-1,2-diphenylethane-1,2-diamine'>RRK</scene>, <scene name='pdbligand=RUD:[ethane6-3-(p-tolyl)propanoic+acid]Ru(1,3,5-triaza-7-phosphaadamantane)Cl2'>RUD</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=5xf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xf3 OCA], [https://pdbe.org/5xf3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xf3 RCSB], [https://www.ebi.ac.uk/pdbsum/5xf3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xf3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/H31_HUMAN H31_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 'acidic patch' is a highly electronegative cleft on the histone H2A-H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis. In vitro, the compounds induce misfolding of chromatin fibre and block the binding of the regulator of chromatin condensation 1 (RCC1) acidic patch-binding protein. This family of chromatin-modifying molecules has potential for applications in drug development and as tools for chromatin research. | |||
Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation.,Davey GE, Adhireksan Z, Ma Z, Riedel T, Sharma D, Padavattan S, Rhodes D, Ludwig A, Sandin S, Murray BS, Dyson PJ, Davey CA Nat Commun. 2017 Nov 17;8(1):1575. doi: 10.1038/s41467-017-01680-4. PMID:29146919<ref>PMID:29146919</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5xf3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Histone 3D structures|Histone 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Adhireksan Z]] | |||
[[Category: Davey CA]] | |||
[[Category: Dyson PJ]] | |||
[[Category: Ma Z]] | |||
[[Category: Murray BS]] | |||
Latest revision as of 11:01, 22 November 2023
Nucleosome core particle with an adduct of a binuclear RAPTA (Ru-arene-phosphaadamantane) compound having a 1,2-diphenylethylenediamine linker (R,R-configuration)Nucleosome core particle with an adduct of a binuclear RAPTA (Ru-arene-phosphaadamantane) compound having a 1,2-diphenylethylenediamine linker (R,R-configuration)
Structural highlights
FunctionPublication Abstract from PubMedThe 'acidic patch' is a highly electronegative cleft on the histone H2A-H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis. In vitro, the compounds induce misfolding of chromatin fibre and block the binding of the regulator of chromatin condensation 1 (RCC1) acidic patch-binding protein. This family of chromatin-modifying molecules has potential for applications in drug development and as tools for chromatin research. Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation.,Davey GE, Adhireksan Z, Ma Z, Riedel T, Sharma D, Padavattan S, Rhodes D, Ludwig A, Sandin S, Murray BS, Dyson PJ, Davey CA Nat Commun. 2017 Nov 17;8(1):1575. doi: 10.1038/s41467-017-01680-4. PMID:29146919[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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