View source for 5fut


==Human choline kinase a1 in complex with compound 4-(dimethylamino)-1-{4-[4-(4-{[4-(pyrrolidin- 1-yl)pyridinium-1-yl]methyl}phenyl)butyl]benzyl}pyridinium (compound BR25)==
<StructureSection load='5fut' size='340' side='right'caption='[[5fut]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fut]] 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=5FUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FUT 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]] 1.6&#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=PQ7:4-(DIMETHYLAMINO)-1-{4-[4-(4-{[4-(PYRROLIDIN-1-YL)PYRIDINIUM-1-YL]METHYL}PHENYL)BUTYL]BENZYL}PYRIDINIUM'>PQ7</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=5fut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fut OCA], [https://pdbe.org/5fut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fut RCSB], [https://www.ebi.ac.uk/pdbsum/5fut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fut 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 ==
Malaria is a life-threatening disease caused by different species of the protozoan parasite Plasmodium, with P. falciparum being the deadliest. Increasing parasitic resistance to existing antimalarials makes the necessity of novel avenues to treat this disease an urgent priority. The enzymes responsible for the synthesis of phosphatidylcholine and phosphatidylethanolamine are attractive drug targets to treat malaria as their selective inhibition leads to an arrest of the parasite's growth and cures malaria in a mouse model. We present here a detailed study that reveals a mode of action for two P. falciparum choline kinase inhibitors both in vitro and in vivo. The compounds present distinct binding modes to the choline/ethanolamine-binding site of P. falciparum choline kinase, reflecting different types of inhibition. Strikingly, these compounds primarily inhibit the ethanolamine kinase activity of the P. falciparum choline kinase, leading to a severe decrease in the phosphatidylethanolamine levels within P. falciparum, which explains the resulting growth phenotype and the parasites death. These studies provide an understanding of the mode of action, and act as a springboard for continued antimalarial development efforts selectively targeting P. falciparum choline kinase.

Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death.,Serran-Aguilera L, Denton H, Rubio-Ruiz B, Lopez-Gutierrez B, Entrena A, Izquierdo L, Smith TK, Conejo-Garcia A, Hurtado-Guerrero R Sci Rep. 2016 Sep 12;6:33189. doi: 10.1038/srep33189. PMID:27616047<ref>PMID:27616047</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5fut" 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: Denton H]]
[[Category: Entrena A]]
[[Category: Hurtado-Guerrero R]]
[[Category: Izquierdo L]]
[[Category: Lopez-Gutierrez B]]
[[Category: Rubio-Ruiz B]]
[[Category: Serran-Aguilera L]]
[[Category: Smith TK]]