View source for 7pnl


==Complex between monomolecular human telomeric G-quadruplex and a sulfonamide derivative of the natural alkaloid Berberine==
<StructureSection load='7pnl' size='340' side='right'caption='[[7pnl]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pnl]] 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=7PNL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PNL 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]] 1.83&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7VE:4-[[1-[3-[(17-methoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.0^{2,10}.0^{4,8}.0^{15,20}]henicosa-1(21),2(10),3,8,13,15,17,19-octaen-16-yl)oxy]propyl]triazol-4-yl]methoxy]benzenesulfonamide'>7VE</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=7pnl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pnl OCA], [https://pdbe.org/7pnl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pnl RCSB], [https://www.ebi.ac.uk/pdbsum/7pnl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pnl ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel class of compounds designed to hit two anti-tumour targets, G-quadruplex structures and human carbonic anhydrases (hCAs) IX and XII is proposed. The induction/stabilisation of G-quadruplex structures by small molecules has emerged as an anticancer strategy, disrupting telomere maintenance and reducing oncogene expression. hCAs IX and XII are well-established anti-tumour targets, upregulated in many hypoxic tumours and contributing to metastasis. The ligands reported feature a berberine G-quadruplex stabiliser scaffold connected to a moiety inhibiting hCAs IX and XII. In vitro experiments showed that our compounds selectively stabilise G-quadruplex structures and inhibit hCAs IX and XII. The crystal structure of a telomeric G-quadruplex in complex with one of these ligands was obtained, shedding light on the ligand/target interaction mode. The most promising ligands showed significant cytotoxicity against CA IX-positive HeLa cancer cells in hypoxia, and the ability to stabilise G-quadruplexes within tumour cells.

Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition.,Nocentini A, Di Porzio A, Bonardi A, Bazzicalupi C, Petreni A, Biver T, Bua S, Marzano S, Amato J, Pagano B, Iaccarino N, De Tito S, Amente S, Supuran CT, Randazzo A, Gratteri P J Enzyme Inhib Med Chem. 2024 Dec;39(1):2366236. doi: , 10.1080/14756366.2024.2366236. Epub 2024 Jun 18. PMID:38905127<ref>PMID:38905127</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7pnl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bazzicalupi C]]
[[Category: Gratteri P]]
[[Category: Nocentini A]]
[[Category: Petreni A]]