4wu9: Difference between revisions
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==Structure of cisPtNAP-NCP145== | ==Structure of cisPtNAP-NCP145== | ||
<StructureSection load='4wu9' size='340' side='right' caption='[[4wu9]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='4wu9' size='340' side='right'caption='[[4wu9]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4wu9]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WU9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4wu9]] 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=4WU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WU9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CX8:[2-{3-[(2-{[2-(AMINO-KAPPAN)ETHYL]AMINO-KAPPAN}ETHYL)AMINO-KAPPAN]PROPYL}-1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONATO(3-)]PLATINUM'>CX8</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"><scene name='pdbligand=CX8:[2-{3-[(2-{[2-(AMINO-KAPPAN)ETHYL]AMINO-KAPPAN}ETHYL)AMINO-KAPPAN]PROPYL}-1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONATO(3-)]PLATINUM'>CX8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wu8|4wu8]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wu8|4wu8]]</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=4wu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wu9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wu9 RCSB], [http://www.ebi.ac.uk/pdbsum/4wu9 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=4wu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wu9 OCA], [http://pdbe.org/4wu9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wu9 RCSB], [http://www.ebi.ac.uk/pdbsum/4wu9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wu9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4wu9" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: African clawed frog]] | |||
[[Category: Large Structures]] | |||
[[Category: Ang, W H]] | [[Category: Ang, W H]] | ||
[[Category: Chin, C F]] | [[Category: Chin, C F]] | ||
Revision as of 11:49, 23 May 2019
Structure of cisPtNAP-NCP145Structure of cisPtNAP-NCP145
Structural highlights
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. [H2A1_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 PubMedPlatinum-based anticancer drugs act therapeutically by forming DNA adducts, but suffer from severe toxicity and resistance problems, which have not been overcome in spite of decades of research. And yet defined chromatin targets have generally not been considered in the drug development process. Here we designed novel platinum-intercalator species to target a highly deformed DNA site near the nucleosome center. Between two seemingly similar structural isomers, we find a striking difference in DNA site selectivity in vitro, which comes about from stereochemical constraints that limit the reactivity of the trans isomer to special DNA sequence elements while still allowing the cis isomer to efficiently form adducts at internal sites in the nucleosome core. This gives the potential for controlling nucleosome site targeting in vivo, which would engender sensitivity to epigenetic distinctions and in particular cell type/status-dependent differences in nucleosome positioning. Moreover, while both compounds yield very similar DNA-adduct structures and display antitumor cell activity rivalling that of cisplatin, the cis isomer, relative to the trans, has a much more rapid cytotoxic effect and distinct impact on cell function. The novel stereochemical principles for controlling DNA site selectivity we discovered could aid in the design of improved site discriminating agents. Stereochemical control of nucleosome targeting by platinum-intercalator antitumor agents.,Chua EY, Davey GE, Chin CF, Droge P, Ang WH, Davey CA Nucleic Acids Res. 2015 Jun 23;43(11):5284-96. doi: 10.1093/nar/gkv356. Epub 2015, Apr 27. PMID:25916851[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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