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5ftg

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Revision as of 07:35, 23 October 2019

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)

Structural highlights

5ftg is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gallego-Ortega D, Ramirez de Molina A, Ramos MA, Valdes-Mora F, Barderas MG, Sarmentero-Estrada J, Lacal JC. Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment. PLoS One. 2009 Nov 12;4(11):e7819. doi: 10.1371/journal.pone.0007819. PMID:19915674 doi:10.1371/journal.pone.0007819
↑ 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. Design, synthesis, crystallization and biological evaluation of new symmetrical biscationic compounds as selective inhibitors of human Choline Kinase alpha1 (ChoKalpha1). Sci Rep. 2016 Mar 31;6:23793. doi: 10.1038/srep23793. PMID:27029499 doi:http://dx.doi.org/10.1038/srep23793

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ftg"

@@ Line 1: / Line 1: @@
 ==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=''>
+<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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FTG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ftg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FTG FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ftg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ftg OCA], [http://pdbe.org/5ftg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ftg RCSB], [http://www.ebi.ac.uk/pdbsum/5ftg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ftg ProSAT]</span></td></tr>
@@ Line 18: / Line 18: @@
 </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: Human]]
+[[Category: Large Structures]]
 [[Category: Baglioni, E]]
 [[Category: Basso, G]]

5ftg

From Proteopedia

Revision as of 07:35, 23 October 2019

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)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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