View source for 6wck


==KRAS G-quadruplex G16T mutant with Bromo Uracil replacing T8 and T16.==
<StructureSection load='6wck' size='340' side='right'caption='[[6wck]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wck]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WCK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WCK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.801&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BRU:5-BROMO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>BRU</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=6wck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wck OCA], [https://pdbe.org/6wck PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wck RCSB], [https://www.ebi.ac.uk/pdbsum/6wck PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wck ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aberrant KRAS signaling is a driver of many cancers and yet remains an elusive target for drug therapy. The nuclease hypersensitive element of the KRAS promoter has been reported to form secondary DNA structures called G-quadruplexes (G4s) which may play important roles in regulating KRAS expression, and has spurred interest in structural elucidation studies of the KRAS G-quadruplexes. Here, we report the first high-resolution crystal structure (1.6 A) of a KRAS G-quadruplex as a 5'-head-to-head dimer with extensive poly-A pi-stacking interactions observed across the dimer. Molecular dynamics simulations confirmed that the poly-A pi-stacking interactions are also maintained in the G4 monomers. Docking and molecular dynamics simulations with two G4 ligands that display high stabilization of the KRAS G4 indicated the poly-A loop was a binding site for these ligands in addition to the 5'-G-tetrad. Given sequence and structural variability in the loop regions provide the opportunity for small-molecule targeting of specific G4s, we envisage this high-resolution crystal structure for the KRAS G-quadruplex will aid in the rational design of ligands to selectively target KRAS.

High resolution crystal structure of a KRAS promoter G-quadruplex reveals a dimer with extensive poly-A pi-stacking interactions for small-molecule recognition.,Ou A, Schmidberger JW, Wilson KA, W Evans C, Hargreaves JA, Grigg M, O'Mara ML, Iyer KS, Bond CS, Smith NM Nucleic Acids Res. 2020 Apr 20. pii: 5822969. doi: 10.1093/nar/gkaa262. PMID:32313953<ref>PMID:32313953</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wck" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bond CS]]
[[Category: Iyer KS]]
[[Category: Ou A]]
[[Category: Schmidberger JW]]
[[Category: Smith NM]]