6v0l

<StructureSection load='6v0l' size='340' side='right'caption='[[6v0l]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[6v0l]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V0L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V0L FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGP:2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>DGP</scene></td></tr>

<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3D1:(2R,3S,5R)-5-(6-AMINO-9H-PURIN-9-YL)-TETRAHYDRO-2-(HYDROXYMETHYL)FURAN-3-OL'>3D1</scene></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=6v0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v0l OCA], [http://pdbe.org/6v0l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v0l RCSB], [http://www.ebi.ac.uk/pdbsum/6v0l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v0l ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

Aberrant expression of PDGFR-beta is associated with a number of diseases. The G-quadruplexes (G4s) formed in PDGFR-beta gene promoter are transcriptional modulators and amenable to small molecule targeting. The major G4 formed in the PDGFR-beta gene promoter was previously shown to have a broken G-strand. Herein, we report that the PDGFR-beta gene promoter sequence forms a vacancy G-quadruplex (vG4) which can be filled in and stabilized by physiologically relevant guanine metabolites, such as dGMP, GMP, and cGMP, as well as guanine-derivative drugs. We determined the NMR structure of the dGMP-fill-in PDGFR-beta vG4 in K(+) solution. This is the first structure of a guanine-metabolite-fill-in vG4 based on a human gene promoter sequence. Our structure and systematic analysis elucidate the contributions of Hoogsten hydrogen bonds, sugar, and phosphate moieties to the specific G-vacancy fill-in. Intriguingly, an equilibrium of 3'- and 5'-end vG4s is present in the PDGFR-beta promoter sequence, and dGMP favors the 5'-end fill-in. Guanine metabolites and drugs were tested and showed a conserved selectivity for the 5'-vacancy, except for cGMP. cGMP binds both the 3'- and 5'-end vG4s and forms two fill-in G4s with similar population. Significantly, guanine metabolites are involved in many physiological and pathological processes in human cells; thus, our results provide a structural basis to understand their potential regulatory functions by interaction with promoter vG4s. Moreover, the NMR structure can guide rational design of ligands that target the PDGFR-beta vG4.

PDGFR-beta Promoter Forms a Vacancy G-Quadruplex that Can Be Filled in by dGMP: Solution Structure and Molecular Recognition of Guanine Metabolites and Drugs.,Wang KB, Dickerhoff J, Wu G, Yang D J Am Chem Soc. 2020 Mar 9. doi: 10.1021/jacs.9b12770. PMID:32101424<ref>PMID:32101424</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 6v0l" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Dickerhoff, J]]

[[Category: Wang, K B]]

[[Category: Wu, G]]

[[Category: Yang, D]]

[[Category: Promoter]]