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==The Solution Structure of the MLN 944-d(TATGCATA)2 Complex==
==The Solution Structure of the MLN 944-d(TATGCATA)2 Complex==
<StructureSection load='4bzu' size='340' side='right'caption='[[4bzu]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
<StructureSection load='4bzu' size='340' side='right'caption='[[4bzu]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4bzu]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BZU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BZU FirstGlance]. <br>
<table><tr><td colspan='2'>[[4bzu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BZU FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bzt|4bzt]], [[4bzv|4bzv]]</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=4bzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bzu OCA], [https://pdbe.org/4bzu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bzu RCSB], [https://www.ebi.ac.uk/pdbsum/4bzu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bzu 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=4bzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bzu OCA], [http://pdbe.org/4bzu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bzu RCSB], [http://www.ebi.ac.uk/pdbsum/4bzu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bzu ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MLN 944 is a bisintercalating DNA-binding antitumor agent known to be a template inhibitor of transcription. Previous (1) H NMR studies of its d(ATGCAT)2 complex concluded that its phenazine chromophores are protonated. However, we find that this is not so, which has important consequences for the charged state of the ligand, for the orientation of its 1-carboxamide group in the complex, and for the details of the interaction of its protonated interchromophore linker with the DNA base pairs. Here, we report a corrected solution structure of the MLN 944-d(ATGCAT)2 complex, and extend the study to complexes with d(TATGCATA)2 , and d(TACGCGTA)2 , using a variety of (1) H and (31) P NMR methods and molecular dynamics simulations employing the AMBER 12 force field. We find that for all three complexes MLN 944 binds as a dication, in which the chromophores are uncharged, in the DNA major groove spanning the central 2 GC base pairs in a manner that maintains the dyad symmetry of the DNA. The carboxamide group lies in the plane of the chromophore, its NH making hydrogen bonding interactions with the phenazine N10 nitrogen, and the protonated linkers form hydrogen bonds with the O6 atom of guanine. The dynamics simulations reveal extensive solvent interactions involving the linker amines, the carboxamide group, and the DNA bases. (c) 2014 Wiley Periodicals, Inc. Biopolymers 101: 1099-1113, 2014.
The solution structure of bis(phenazine-1-carboxamide)-DNA complexes: MLN 944 binding corrected and extended.,Serobian A, Thomas DS, Ball GE, Denny WA, Wakelin LP Biopolymers. 2014 Nov;101(11):1099-113. doi: 10.1002/bip.22513. PMID:24898663<ref>PMID:24898663</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bzu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Ball, G E]]
[[Category: Synthetic construct]]
[[Category: Denny, W A]]
[[Category: Ball GE]]
[[Category: Serobian, A]]
[[Category: Denny WA]]
[[Category: Thomas, D S]]
[[Category: Serobian A]]
[[Category: Wakelin, L P.G]]
[[Category: Thomas DS]]
[[Category: Anticancer drug]]
[[Category: Wakelin LPG]]
[[Category: Dna]]
[[Category: Drug design]]
[[Category: Intercalation]]
[[Category: Mln 944]]

Latest revision as of 17:18, 7 September 2022

The Solution Structure of the MLN 944-d(TATGCATA)2 Complex

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