View source for 5dnm


==Nucleosome core particle containing adducts of ruthenium(II)-toluene PTA complex==
<StructureSection load='5dnm' size='340' side='right'caption='[[5dnm]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5dnm]] 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=5DNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DNM 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]] 2.81&#8491;</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=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=5dnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dnm OCA], [https://pdbe.org/5dnm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dnm RCSB], [https://www.ebi.ac.uk/pdbsum/5dnm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dnm ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated by allosteric cross-talk in chromatin, whereby the binding of one drug alters the activity of the second. We found two unrelated drugs, RAPTA-T and auranofin, that yield a synergistic activity in killing cancer cells, which coincides with a substantially greater number of chromatin adducts formed by one of the compounds when adducts from the other agent are also present. We show that this occurs through an allosteric mechanism within the nucleosome, whereby defined histone adducts of one drug promote reaction of the other drug at a distant, specific histone site. This opens up possibilities for epigenetic targeting and suggests that allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions.

Allosteric cross-talk in chromatin can mediate drug-drug synergy.,Adhireksan Z, Palermo G, Riedel T, Ma Z, Muhammad R, Rothlisberger U, Dyson PJ, Davey CA Nat Commun. 2017 Mar 30;8:14860. doi: 10.1038/ncomms14860. PMID:28358030<ref>PMID:28358030</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5dnm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone 3D structures|Histone 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Xenopus laevis]]
[[Category: Adhireksan Z]]
[[Category: Davey CA]]
[[Category: Muhammad R]]