4cga: Difference between revisions
No edit summary |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Human choline kinase a1 in complex with compound 5== | ==Human choline kinase a1 in complex with compound 5== | ||
<StructureSection load='4cga' size='340' side='right' caption='[[4cga]], [[Resolution|resolution]] 1.74Å' scene=''> | <StructureSection load='4cga' size='340' side='right'caption='[[4cga]], [[Resolution|resolution]] 1.74Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cga]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4cga]] 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=4CGA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CGA FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.74Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QLW:N,N-DIMETHYL-1-[[4-(2-PHENYLETHYL)PHENYL]METHYL]PYRIDIN-1-IUM-4-AMINE'>QLW</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cga FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cga OCA], [https://pdbe.org/4cga PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cga RCSB], [https://www.ebi.ac.uk/pdbsum/4cga PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cga ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 17: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4cga" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Choline kinase|Choline kinase]] | *[[Choline kinase 3D structures|Choline kinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Capitan-Canadas | [[Category: Large Structures]] | ||
[[Category: Carrasco | [[Category: Capitan-Canadas F]] | ||
[[Category: Concepcion | [[Category: Carrasco MP]] | ||
[[Category: Conejo-Garcia | [[Category: Concepcion C]] | ||
[[Category: Entrena-Guadix | [[Category: Conejo-Garcia A]] | ||
[[Category: Espinosa | [[Category: Entrena-Guadix A]] | ||
[[Category: Figuerola-Conchas | [[Category: Espinosa A]] | ||
[[Category: Gallo | [[Category: Figuerola-Conchas A]] | ||
[[Category: Hurtado-Guerrero | [[Category: Gallo MA]] | ||
[[Category: Marco | [[Category: Hurtado-Guerrero R]] | ||
[[Category: Ramos-Torrecillas | [[Category: Marco C]] | ||
[[Category: Rios-Marco | [[Category: Ramos-Torrecillas J]] | ||
[[Category: Rubio-Ruiz | [[Category: Rios-Marco P]] | ||
[[Category: Rubio-Ruiz B]] | |||
Latest revision as of 15:09, 20 December 2023
Human choline kinase a1 in complex with compound 5Human choline kinase a1 in complex with compound 5
Structural highlights
FunctionCHKA_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 PubMedHuman 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||