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4kgc

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Revision as of 16:22, 5 August 2016

Nucleosome Core Particle Containing (ETA6-P-CYMENE)-(1, 2-ETHYLENEDIAMINE)-RUTHENIUM

Structural highlights

4kgc is a 10 chain structure with sequence from African clawed frog. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	hist1h2aj, LOC494591 (African clawed frog)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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. [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. [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.

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kgc"

@@ Line 1: / Line 1: @@
 ==Nucleosome Core Particle Containing (ETA6-P-CYMENE)-(1, 2-ETHYLENEDIAMINE)-RUTHENIUM==
 <StructureSection load='4kgc' size='340' side='right' caption='[[4kgc]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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>
 <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'>[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://www.rcsb.org/pdb/explore.do?structureId=4kgc RCSB], [http://www.ebi.ac.uk/pdbsum/4kgc PDBsum]</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>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4kgc" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Histone|Histone]]
 == References ==
 <references/>

4kgc

From Proteopedia

Revision as of 16:22, 5 August 2016

Nucleosome Core Particle Containing (ETA6-P-CYMENE)-(1, 2-ETHYLENEDIAMINE)-RUTHENIUM

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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