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| | ==Nucleosome Core Particle Containing (ETA6-P-CYMENE)-(1, 2-ETHYLENEDIAMINE)-RUTHENIUM== | | ==Nucleosome Core Particle Containing (ETA6-P-CYMENE)-(1, 2-ETHYLENEDIAMINE)-RUTHENIUM== |
| - | <StructureSection load='4kgc' size='340' side='right' caption='[[4kgc]], [[Resolution|resolution]] 2.69Å' scene=''> | + | <StructureSection load='4kgc' size='340' side='right'caption='[[4kgc]], [[Resolution|resolution]] 2.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kgc]] 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=4KGC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KGC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kgc]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KGC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HRU:(ETHANE-1,2-DIAMINE-KAPPA~2~N,N)[(1,2,3,4,5,6-ETA)-1-METHYL-4-(PROPAN-2-YL)CYCLOHEXANE-1,2,3,4,5,6-HEXAYL]RUTHENIUM'>HRU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HRU:(ETHANE-1,2-DIAMINE-KAPPA~2~N,N)[(1,2,3,4,5,6-ETA)-1-METHYL-4-(PROPAN-2-YL)CYCLOHEXANE-1,2,3,4,5,6-HEXAYL]RUTHENIUM'>HRU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4kgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kgc OCA], [https://pdbe.org/4kgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kgc RCSB], [https://www.ebi.ac.uk/pdbsum/4kgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kgc 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=4kgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kgc OCA], [http://pdbe.org/4kgc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kgc RCSB], [http://www.ebi.ac.uk/pdbsum/4kgc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kgc 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 4kgc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4kgc" 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: Large Structures]] |
| - | [[Category: Adhireksan, Z]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Davey, C A]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Dna-protein complex]] | + | [[Category: Adhireksan Z]] |
| - | [[Category: Nucleosome]] | + | [[Category: Davey CA]] |
| - | [[Category: Ruthenium agent]]
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| - | [[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
Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favourable toxicity and clearance properties. Nonetheless, their molecular targeting and mechanism of action are poorly understood. Here we study two prototypical ruthenium-arene agents-the cytotoxic antiprimary tumour compound [(eta(6)-p-cymene)Ru(ethylene-diamine)Cl]PF6 and the relatively non-cytotoxic antimetastasis compound [(eta(6)-p-cymene)Ru(1,3,5-triaza-7-phosphaadamantane)Cl2]-and discover that the former targets the DNA of chromatin, while the latter preferentially forms adducts on the histone proteins. Using a novel 'atom-to-cell' approach, we establish the basis for the surprisingly site-selective adduct formation behaviour and distinct cellular impact of these two chemically similar anticancer agents, which suggests that the cytotoxic effects arise largely from DNA lesions, whereas the protein adducts may be linked to the other therapeutic activities. Our study shows promise for developing new ruthenium drugs, via ligand-based modulation of DNA versus protein binding and thus cytotoxic potential, to target distinguishing epigenetic features of cancer cells.
Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity.,Adhireksan Z, Davey GE, Campomanes P, Groessl M, Clavel CM, Yu H, Nazarov AA, Yeo CH, Ang WH, Droge P, Rothlisberger U, Dyson PJ, Davey CA Nat Commun. 2014 Mar 18;5:3462. doi: 10.1038/ncomms4462. PMID:24637564[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Adhireksan Z, Davey GE, Campomanes P, Groessl M, Clavel CM, Yu H, Nazarov AA, Yeo CH, Ang WH, Droge P, Rothlisberger U, Dyson PJ, Davey CA. Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity. Nat Commun. 2014 Mar 18;5:3462. doi: 10.1038/ncomms4462. PMID:24637564 doi:http://dx.doi.org/10.1038/ncomms4462
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