View source for 6jj0


==NMR structure of the 1:1 complex of a carbazole derivative BMVC bound to c-MYC G-quadruplex==
<StructureSection load='6jj0' size='340' side='right'caption='[[6jj0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jj0]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JJ0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BO6:3,6-bis[(E)-2-(1-methylpyridin-1-ium-4-yl)ethenyl]-9H-carbazole'>BO6</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=6jj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jj0 OCA], [https://pdbe.org/6jj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jj0 RCSB], [https://www.ebi.ac.uk/pdbsum/6jj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jj0 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BMVC is the first fluorescent probe designed to detect G-quadruplexes (G4s) in vivo. The MYC oncogene promoter forms a G4 (MycG4) which acts as a transcription silencer. Here, we report the high-affinity and specific binding of BMVC to MycG4 with unusual slow-exchange rates on the NMR timescale. We also show that BMVC represses MYC in cancer cells. We determined the solution structures of the 1:1 and 2:1 BMVC-MycG4 complexes. BMVC first binds the 5'-end of MycG4 to form a 1:1 complex with a well-defined structure. At higher ratio, BMVC also binds the 3'-end to form a second complex. In both complexes, the crescent-shaped BMVC recruits a flanking DNA residue to form a BMVC-base plane stacking over the external G-tetrad. Remarkably, BMVC adjusts its conformation to a contracted form to match the G-tetrad for an optimal stacking interaction. This is the first structural example showing the importance of ligand conformational adjustment in G4 recognition. BMVC binds the more accessible 5'-end with higher affinity, whereas sequence specificity is present at the weaker-binding 3'-site. Our structures provide insights into specific recognition of MycG4 by BMVC and useful information for design of G4-targeted anticancer drugs and fluorescent probes.

Structures of 1:1 and 2:1 complexes of BMVC and MYC promoter G-quadruplex reveal a mechanism of ligand conformation adjustment for G4-recognition.,Liu W, Lin C, Wu G, Dai J, Chang TC, Yang D Nucleic Acids Res. 2019 Dec 16;47(22):11931-11942. doi: 10.1093/nar/gkz1015. PMID:31740959<ref>PMID:31740959</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jj0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lin, C]]
[[Category: Liu, W]]
[[Category: Yang, D]]
[[Category: Bmvc]]
[[Category: Dna]]
[[Category: Drug-dna complex]]
[[Category: G-quadruplex dna]]