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| | ==Nucleosome core particle with an adduct of a binuclear RAPTA (Ru-arene-phosphaadamantane) compound having an ethylenediamine linker== | | ==Nucleosome core particle with an adduct of a binuclear RAPTA (Ru-arene-phosphaadamantane) compound having an ethylenediamine linker== |
| - | <StructureSection load='5xf6' size='340' side='right' caption='[[5xf6]], [[Resolution|resolution]] 2.63Å' scene=''> | + | <StructureSection load='5xf6' size='340' side='right'caption='[[5xf6]], [[Resolution|resolution]] 2.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xf6]] is a 10 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=5XF6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XF6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xf6]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XF6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDN:ETHANE-1,2-DIAMINE'>EDN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.63Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5xf3|5xf3]], [[5xf4|5xf4]], [[5xf5|5xf5]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDN:ETHANE-1,2-DIAMINE'>EDN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hist1h2aj, LOC494591 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5xf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xf6 OCA], [https://pdbe.org/5xf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xf6 RCSB], [https://www.ebi.ac.uk/pdbsum/5xf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xf6 ProSAT]</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=5xf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xf6 OCA], [http://pdbe.org/5xf6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xf6 RCSB], [http://www.ebi.ac.uk/pdbsum/5xf6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xf6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/H2B11_XENLA H2B11_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/H32_XENLA H32_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/H4_XENLA H4_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. | + | [https://www.uniprot.org/uniprot/H32_XENLA H32_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5xf6" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5xf6" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Histone 3D structures|Histone 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: African clawed frog]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Adhireksan, Z]] | + | [[Category: Large Structures]] |
| - | [[Category: Davey, C A]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Dyson, P J]] | + | [[Category: Adhireksan Z]] |
| - | [[Category: Ma, Z]]
| + | [[Category: Davey CA]] |
| - | [[Category: Murray, B S]] | + | [[Category: Dyson PJ]] |
| - | [[Category: Binuclear metal-based agent]] | + | [[Category: Ma Z]] |
| - | [[Category: Histone adduct]] | + | [[Category: Murray BS]] |
| - | [[Category: Nucleosome]] | + | |
| - | [[Category: Ruthenium compound]]
| + | |
| - | [[Category: Structural protein-dna complex]]
| + | |
| Structural highlights
Function
H32_XENLA Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Davey GE, Adhireksan Z, Ma Z, Riedel T, Sharma D, Padavattan S, Rhodes D, Ludwig A, Sandin S, Murray BS, Dyson PJ, Davey CA. Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation. Nat Commun. 2017 Nov 17;8(1):1575. doi: 10.1038/s41467-017-01680-4. PMID:29146919 doi:http://dx.doi.org/10.1038/s41467-017-01680-4
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