View source for 4cg8


==Human choline kinase a1 in complex with compound 14==
<StructureSection load='4cg8' size='340' side='right'caption='[[4cg8]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cg8]] 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=4CG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CG8 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G8S:4-[(4-CHLOROPHENYL)(METHYL)AMINO]-1-{4-[4-(4-{[4-(DIMETHYLAMINO)PYRIDINIUM-1-YL]METHYL}PHENYL)BUTYL]BENZYL}PYRIDINIUM'>G8S</scene>, <scene name='pdbligand=G8V:1-BENZYL-4-(DIMETHYLAMINO)PYRIDINIUM'>G8V</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=4cg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cg8 OCA], [https://pdbe.org/4cg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cg8 RCSB], [https://www.ebi.ac.uk/pdbsum/4cg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cg8 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 ==
Human choline kinase alpha (CKalpha) is a validated drug target for the treatment of cancer. In recent years, a large number of CK inhibitors have been synthesized, and one of them is currently being evaluated in Phase I clinical trials as a treatment for solid tumors. Here we have evaluated a new series of asymmetrical biscationic CK inhibitors by means of enzymatic, crystallographic, and antitumor studies. We demonstrate that one of these structures adopts a completely new binding mode not observed before inducing the aperture of an adjacent binding site. This compound shows antiproliferative and apoptotic effects on cancer cells through activation of caspase-3. Therefore, this study not only provides fruitful insights into the design of more efficient compounds that may target different regions in CKalpha1 but also explains how these compounds induce apoptosis in cancer cells.

Discovery of a New Binding Site on Human Choline Kinase alpha1: Design, Synthesis, Crystallographic Studies, and Biological Evaluation of Asymmetrical Bispyridinium Derivatives.,Rubio-Ruiz B, Figuerola-Conchas A, Ramos-Torrecillas J, Capitan-Canadas F, Rios-Marco P, Carrasco MP, Gallo MA, Espinosa A, Marco C, Ruiz C, Entrena A, Hurtado-Guerrero R, Conejo-Garcia A J Med Chem. 2014 Jan 14. PMID:24387243<ref>PMID:24387243</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cg8" 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: Conejo-Garcia A]]
[[Category: Entrena-Guadix A]]
[[Category: Figuerola-Conchas A]]
[[Category: Hurtado-Guerrero R]]
[[Category: Rubio-Ruiz B]]