View source for 5eqy


==Crystal structure of choline kinase alpha-1 bound by 5-[(4-methyl-1,4-diazepan-1-yl)methyl]-2-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]benzenecarbonitrile (compound 65)==
<StructureSection load='5eqy' size='340' side='right'caption='[[5eqy]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5eqy]] is a 2 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=5EQY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EQY 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5RA:5-[(4-METHYL-1,4-DIAZEPAN-1-YL)METHYL]-2-[4-[(4-METHYL-1,4-DIAZEPAN-1-YL)METHYL]PHENYL]BENZENECARBONITRILE'>5RA</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=5eqy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eqy OCA], [https://pdbe.org/5eqy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eqy RCSB], [https://www.ebi.ac.uk/pdbsum/5eqy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eqy 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 ==
Choline kinase alpha (ChoKalpha) is an enzyme involved in the synthesis of phospholipids, and thereby plays key roles in regulation of cell proliferation, oncogenic transformation and human carcinogenesis. Since several inhibitors of ChoKalpha display anti-proliferative activity in both cellular and animal models, this novel oncogene has recently gained interest as a promising small molecule target for cancer therapy. Here we summarize our efforts to further validate ChoKalpha as an oncogenic target, and explore the activity of novel small molecule inhibitors of ChoKalpha. Starting from weakly binding fragments, we describe a structure based lead discovery approach, which resulted in novel highly potent inhibitors of ChoKalpha. In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phosphocholine, inhibition of cell growth and induction of apoptosis at low micromolar concentrations. The drug-like lead series presented here is optimizable for improvements in cellular potency, drug target residence time, and pharmacokinetic parameters. These inhibitors may be utilized not only to further validate ChoKalpha as anti-oncogenic target, but also as novel chemical matter which may lead to anti-tumor agents that specifically interfere with cancer cell metabolism.

Novel Small Molecule Inhibitors of Choline Kinase Identified by Fragment-based Drug Discovery.,Zech SG, Kohlmann A, Zhou T, Li F, Squillache R, Parillon L, Greenfield M, Miller D, Qi J, Thomas M, Wang Y, Xu Y, Miret J, Shakespeare WC, Zhu X, Dalgarno DC J Med Chem. 2015 Dec 23. PMID:26700752<ref>PMID:26700752</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5eqy" 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: Dalgarno DC]]
[[Category: Zhou T]]
[[Category: Zhu X]]