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==Solution structure of the MYC promoter G-quadruplex in complex with berberine: conformer B== | |||
<StructureSection load='7n7e' size='340' side='right'caption='[[7n7e]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7n7e]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N7E FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BER:BERBERINE'>BER</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7n7d|7n7d]]</div></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=7n7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n7e OCA], [https://pdbe.org/7n7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n7e RCSB], [https://www.ebi.ac.uk/pdbsum/7n7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n7e ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The medicinal natural product berberine is one of the most actively studied and pursued G-quadruplex (G4)-ligands. The major G-quadruplex formed in the promoter region of the MYC oncogene (MycG4) is an attractive drug target and a prominent example and model structure for parallel G-quadruplexes. G4-targeted berberine derivatives have been actively developed; however, the analogue design was based on a previous crystal structure in which berberine binds as a dimer to a parallel G-quadruplex. Herein, we show that in solution, the binding mode and stoichiometry of berberine are substantially different from the crystal structure: berberine binds as a monomer to MycG4 using a base-recruitment mechanism with a reversed orientation in that the positively charged convex side is actually positioned above the tetrad center. Our structure provides a physiologically relevant basis for the future structure-based rational design of G4-targeted berberine derivatives, and this study demonstrates that it is crucial to validate the ligand-DNA interactions. | |||
Berberine Molecular Recognition of the Parallel MYC G-Quadruplex in Solution.,Dickerhoff J, Brundridge N, McLuckey SA, Yang D J Med Chem. 2021 Oct 22. doi: 10.1021/acs.jmedchem.1c01508. PMID:34677968<ref>PMID:34677968</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7n7e" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Dickerhoff, J]] | |||
[[Category: Yang, D]] | |||
[[Category: Berberine]] | |||
[[Category: Cancer]] | |||
[[Category: Dna]] | |||
[[Category: Drug-dna complex]] | |||
[[Category: G-quadruplex dna]] | |||
Latest revision as of 15:46, 24 November 2021
Solution structure of the MYC promoter G-quadruplex in complex with berberine: conformer BSolution structure of the MYC promoter G-quadruplex in complex with berberine: conformer B
Structural highlights
Publication Abstract from PubMedThe medicinal natural product berberine is one of the most actively studied and pursued G-quadruplex (G4)-ligands. The major G-quadruplex formed in the promoter region of the MYC oncogene (MycG4) is an attractive drug target and a prominent example and model structure for parallel G-quadruplexes. G4-targeted berberine derivatives have been actively developed; however, the analogue design was based on a previous crystal structure in which berberine binds as a dimer to a parallel G-quadruplex. Herein, we show that in solution, the binding mode and stoichiometry of berberine are substantially different from the crystal structure: berberine binds as a monomer to MycG4 using a base-recruitment mechanism with a reversed orientation in that the positively charged convex side is actually positioned above the tetrad center. Our structure provides a physiologically relevant basis for the future structure-based rational design of G4-targeted berberine derivatives, and this study demonstrates that it is crucial to validate the ligand-DNA interactions. Berberine Molecular Recognition of the Parallel MYC G-Quadruplex in Solution.,Dickerhoff J, Brundridge N, McLuckey SA, Yang D J Med Chem. 2021 Oct 22. doi: 10.1021/acs.jmedchem.1c01508. PMID:34677968[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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