View source for 5w77


==Solution structure of the MYC G-quadruplex bound to small molecule DC-34==
<StructureSection load='5w77' size='340' side='right'caption='[[5w77]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5w77]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W77 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9WP:4-[(azepan-1-yl)methyl]-5-hydroxy-2-methyl-N-[4-(trifluoromethyl)phenyl]-1-benzofuran-3-carboxamide'>9WP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=5w77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w77 OCA], [https://pdbe.org/5w77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w77 RCSB], [https://www.ebi.ac.uk/pdbsum/5w77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w77 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
G-quadruplexes (G4s) are noncanonical DNA structures that frequently occur in the promoter regions of oncogenes, such as MYC, and regulate gene expression. Although G4s are attractive therapeutic targets, ligands capable of discriminating between different G4 structures are rare. Here, we describe DC-34, a small molecule that potently downregulates MYC transcription in cancer cells by a G4-dependent mechanism. Inhibition by DC-34 is significantly greater for MYC than other G4-driven genes. We use chemical, biophysical, biological, and structural studies to demonstrate a molecular rationale for the recognition of the MYC G4. We solve the structure of the MYC G4 in complex with DC-34 by NMR spectroscopy and illustrate specific contacts responsible for affinity and selectivity. Modification of DC-34 reveals features required for G4 affinity, biological activity, and validates the derived NMR structure. This work advances the design of quadruplex-interacting small molecules to control gene expression in therapeutic areas such as cancer.

Chemical and structural studies provide a mechanistic basis for recognition of the MYC G-quadruplex.,Calabrese DR, Chen X, Leon EC, Gaikwad SM, Phyo Z, Hewitt WM, Alden S, Hilimire TA, He F, Michalowski AM, Simmons JK, Saunders LB, Zhang S, Connors D, Walters KJ, Mock BA, Schneekloth JS Jr Nat Commun. 2018 Oct 12;9(1):4229. doi: 10.1038/s41467-018-06315-w. PMID:30315240<ref>PMID:30315240</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5w77" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen X]]
[[Category: Walters KJ]]