View source for 6s15


==Pyridine derivative of the natural alkaloid Berberine as Human Telomeric G-quadruplex Binder==
<StructureSection load='6s15' size='340' side='right'caption='[[6s15]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6s15]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6S15 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]] 1.7&#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=KQT:Berberine'>KQT</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=6s15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s15 OCA], [https://pdbe.org/6s15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6s15 RCSB], [https://www.ebi.ac.uk/pdbsum/6s15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6s15 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Telomerase is an enzyme deputed to the maintenance of eukaryotic chromosomes; however, its overexpression is a recognized hallmark of many cancer forms. A viable route for the inhibition of telomerase in malignant cells is the stabilization of G-quadruplex structures (G(4)) at the 3' overhang of telomeres. Berberine has shown in this regard valuable G(4) binding properties together with a significant anticancer activity and telomerase inhibition effects. Here, we focused on a berberine derivative featuring a pyridine containing side group at the 13th position. Such modification actually improves the binding toward telomeric G-quadruplexes and establishes a degree of selectivity in the interaction with different sequences. Moreover, the X-ray crystal structure obtained for the complex formed by the ligand and a bimolecular human telomeric quadruplex affords a better understanding of the 13-berberine derivatives behavior with telomeric G(4) and allows to draw useful insights for the future design of derivatives with remarkable anticancer properties.

Pyridine Derivative of the Natural Alkaloid Berberine as Human Telomeric G(4)-DNA Binder: A Solution and Solid-State Study.,Papi F, Bazzicalupi C, Ferraroni M, Ciolli G, Lombardi P, Khan AY, Kumar GS, Gratteri P ACS Med Chem Lett. 2020 Feb 7;11(5):645-650. doi: 10.1021/acsmedchemlett.9b00516. , eCollection 2020 May 14. PMID:32435365<ref>PMID:32435365</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6s15" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Bazzicalupi C]]
[[Category: Ferraroni M]]
[[Category: Gratteri P]]
[[Category: Papi F]]