View source for 5ftg


==Human choline kinase a1 in complex with compound 1-[[4-[2-[4-[[4-(dimethylamino)pyridin-1- yl]methyl]phenoxy]ethoxy]phenyl]methyl]-N,N- dimethyl-pyridin-4-amine (compound 10a)==
<StructureSection load='5ftg' size='340' side='right'caption='[[5ftg]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ftg]] 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=5FTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FTG 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]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NBR:1-[[4-[2-[4-[[4-(DIMETHYLAMINO)PYRIDIN-1-YL]METHYL]PHENOXY]ETHOXY]PHENYL]METHYL]-N,N-DIMETHYL-PYRIDIN-4-AMINE'>NBR</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=5ftg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ftg OCA], [https://pdbe.org/5ftg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ftg RCSB], [https://www.ebi.ac.uk/pdbsum/5ftg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ftg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHKA_HUMAN CHKA_HUMAN] Has a key role in phospholipid biosynthesis and may contribute to tumor cell growth. Catalyzes the first step in phosphatidylcholine biosynthesis. Contributes to phosphatidylethanolamine biosynthesis. Phosphorylates choline and ethanolamine. Has higher activity with choline.<ref>PMID:19915674</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel family of compounds derivative of 1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))-bispyridinium or -bisquinolinium bromide (10a-l) containing a pair of oxygen atoms in the spacer of the linker between the biscationic moieties, were synthesized and evaluated as inhibitors of choline kinase against a panel of cancer-cell lines. The most promising compounds in this series were 1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))bis(4-(dimethyl amino)pyridinium) bromide (10a) and 1,1'-(((ethane-1,2-diylbis(oxy))bis(4,1-phenylene))bis(methylene))-bis(7-chloro-4 -(pyrrolidin-1-yl)quinolinium) bromide (10l), which inhibit human choline kinase (ChoKalpha1) with IC50 of 1.0 and 0.92 muM, respectively, in a range similar to that of the previously reported biscationic compounds MN58b and RSM932A. Our compounds show greater antiproliferative activities than do the reference compounds, with unprecedented values of GI50 in the nanomolar range for several of the cancer-cell lines assayed, and more importantly they present low toxicity in non-tumoral cell lines, suggesting a cancer-cell-selective antiproliferative activity. Docking studies predict that the compounds interact with the choline-binding site in agreement with the binding mode of most previously reported biscationic compounds. Moreover, the crystal structure of ChoKalpha1 with compound 10a reveals that this compound binds to the choline-binding site and mimics HC-3 binding mode as never before.

Design, synthesis, crystallization and biological evaluation of new symmetrical biscationic compounds as selective inhibitors of human Choline Kinase alpha1 (ChoKalpha1).,Schiaffino-Ortega S, Baglioni E, Mariotto E, Bortolozzi R, Serran-Aguilera L, Rios-Marco P, Carrasco-Jimenez MP, Gallo MA, Hurtado-Guerrero R, Marco C, Basso G, Viola G, Entrena A, Lopez-Cara LC Sci Rep. 2016 Mar 31;6:23793. doi: 10.1038/srep23793. PMID:27029499<ref>PMID:27029499</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ftg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Choline kinase 3D structures|Choline kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baglioni E]]
[[Category: Basso G]]
[[Category: Bortolozzi R]]
[[Category: Carrasco-Jimenez MP]]
[[Category: Entrena A]]
[[Category: Gallo MA]]
[[Category: Hurtado-Guerrero R]]
[[Category: Lopez-Cara LC]]
[[Category: Marco C]]
[[Category: Mariotto E]]
[[Category: Rios-Marco P]]
[[Category: Schiaffino-Ortega S]]
[[Category: Serran-Aguilera L]]
[[Category: Viola G]]