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==Solution structure of TFF1 Estrogen Response Element complexed with DNA Bis-intercalating Anticancer Drug XR5944 (MLN944)==
==Solution structure of TFF1 Estrogen Response Element complexed with DNA Bis-intercalating Anticancer Drug XR5944 (MLN944)==
<StructureSection load='2mg8' size='340' side='right'caption='[[2mg8]], [[NMR_Ensembles_of_Models | 14 NMR models]]' scene=''>
<StructureSection load='2mg8' size='340' side='right'caption='[[2mg8]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2mg8]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MG8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2mg8]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MG8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XR2:1-METHYL-9-[12-(9-METHYLPHENAZIN-10-IUM-1-YL)-12-OXO-2,11-DIAZA-5,8-DIAZONIADODEC-1-ANOYL]PHENAZIN-10-IUM'>XR2</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1x95|1x95]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XR2:1-METHYL-9-[12-(9-METHYLPHENAZIN-10-IUM-1-YL)-12-OXO-2,11-DIAZA-5,8-DIAZONIADODEC-1-ANOYL]PHENAZIN-10-IUM'>XR2</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=2mg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mg8 OCA], [https://pdbe.org/2mg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mg8 RCSB], [https://www.ebi.ac.uk/pdbsum/2mg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mg8 ProSAT]</span></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=2mg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mg8 OCA], [https://pdbe.org/2mg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mg8 RCSB], [https://www.ebi.ac.uk/pdbsum/2mg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mg8 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
XR5944, a deoxyribonucleic acid (DNA) bis-intercalator with potent anticancer activity, can bind the estrogen response element (ERE) sequence to inhibit estrogen receptor-alpha activities. This novel mechanism of action may be useful for overcoming drug resistance to currently available antiestrogen treatments, all of which target the hormone-receptor complex. Here we report the nuclear magnetic resonance solution structure of the 2:1 complex of XR5944 with the naturally occurring TFF1-ERE, which exhibits important and unexpected features. In both drug-DNA complexes, XR5944 binds strongly at one intercalation site but weakly at the second site. The sites of intercalation within a native promoter sequence appear to be context and sequence dependent. The binding of one drug molecule influences the binding site of the second. Our structures underscore the fact that the DNA binding of a bis-intercalator is directional and different from the simple addition of two single intercalation sites. Our study suggests that improved XR5944 bis-intercalators targeting ERE may be designed through optimization of aminoalkyl linker and intercalation moieties at the weak binding sites.
Solution structure of a 2:1 complex of anticancer drug XR5944 with TFF1 estrogen response element: insights into DNA recognition by a bis-intercalator.,Lin C, Mathad RI, Zhang Z, Sidell N, Yang D Nucleic Acids Res. 2014 Apr 7. PMID:24711371<ref>PMID:24711371</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mg8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lin, C]]
[[Category: Lin C]]
[[Category: Breast cancer drug]]
[[Category: Dna]]
[[Category: Dna bis-intercalation]]
[[Category: Ere-targeting small molecule anticancer drug]]

Latest revision as of 10:00, 1 May 2024

Solution structure of TFF1 Estrogen Response Element complexed with DNA Bis-intercalating Anticancer Drug XR5944 (MLN944)Solution structure of TFF1 Estrogen Response Element complexed with DNA Bis-intercalating Anticancer Drug XR5944 (MLN944)

Structural highlights

2mg8 is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT
Drag the structure with the mouse to rotate

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OCA
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