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==Crystal structure of a three-tetrad, parallel, and K+ stabilized homopurine G-quadruplex from human chromosome 7==
<StructureSection load='8edp' size='340' side='right'caption='[[8edp]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8edp]] is a 1 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=8EDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EDP 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]] 2.01&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MMP:N-METHYLMESOPORPHYRIN'>MMP</scene>, <scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</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=8edp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8edp OCA], [https://pdbe.org/8edp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8edp RCSB], [https://www.ebi.ac.uk/pdbsum/8edp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8edp ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA can fold into G-quadruplexes (GQs), non-canonical secondary structures formed by pi-pi stacking of G-tetrads. GQs are important in many biological processes, which makes them promising therapeutic targets. We identified a 42-nucleotide long, purine-only G-rich sequence from human genome, which contains eight G-stretches connected by A and AAAA loops. We divided this sequence into five unique segments, four guanine stretches each, named GA1-5. In order to investigate the role of adenines in GQ structure formation, we performed biophysical and X-ray crystallographic studies of GA1-5 and their complexes with a highly selective GQ ligand, N-methyl mesoporphyrin IX (NMM). Our data indicate that all variants form parallel GQs whose stability depends on the number of flexible AAAA loops. GA1-3 bind NMM with 1:1 stoichiometry. The K(a) for GA1 and GA3 is modest, approximately 0.3 muM (-)(1), and that for GA2 is significantly higher, approximately 1.2 muM (-)(1). NMM stabilizes GA1-3 by 14.6, 13.1, and 7.0 degrees C, respectively, at 2 equivalents. We determined X-ray crystal structures of GA1-NMM (1.98 A resolution) and GA3-NMM (2.01 A). The structures confirm the parallel topology of GQs with all adenines forming loops and display NMM binding at the 3' G-tetrad. Both complexes dimerize through the 5' interface. We observe two novel structural features: 1) a 'symmetry tetrad' at the dimer interface, which is formed by two guanines from each GQ monomer and 2) a NMM dimer in GA1-NMM. Our structural work confirms great flexibility of adenines as structural elements in GQ formation and contributes greatly to our understanding of the structural diversity of GQs and their modes of interaction with small molecule ligands.

Homopurine guanine-rich sequences in complex with N-methyl mesoporphyrin IX form parallel G-quadruplex dimers and display a unique symmetry tetrad.,Ye M, Chen EV, Pfeil SH, Martin KN, Atrafi T, Yun S, Martinez Z, Yatsunyk LA Bioorg Med Chem. 2023 Jan 1;77:117112. doi: 10.1016/j.bmc.2022.117112. Epub 2022 , Dec 1. PMID:36508994<ref>PMID:36508994</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8edp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Yatsunyk LA]]
[[Category: Ye M]]