7a04: Difference between revisions
New page: '''Unreleased structure''' The entry 7a04 is ON HOLD Authors: Serran-Aguilera, L., Mariotto, E., Rubbini, G., Castro Navas, F.C., Marco, C., Carrasco-Jimenez, M.P., Ballarotto, M., Macc... |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Structure of human CKa1 in complex with compound b== | |||
<StructureSection load='7a04' size='340' side='right'caption='[[7a04]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7a04]] 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=7A04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A04 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]] 2.15Å</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=QTK:1-(phenylmethyl)-4-pyrrolidin-1-yl-pyridin-1-ium'>QTK</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=7a04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a04 OCA], [https://pdbe.org/7a04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a04 RCSB], [https://www.ebi.ac.uk/pdbsum/7a04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a04 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 == | |||
Seeking for new anticancer drugs with strong antiproliferative activity and simple molecular structure, we designed a novel series of compounds based on our previous reported pharmacophore model composed of five moieties. Antiproliferative assays on four tumoral cell lines and evaluation of Human Choline Kinase CKalpha1 enzymatic activity was performed for these compounds. Among tested molecules, those ones with biphenyl spacer showed betters enzymatic and antiproliferative activities (n-v). Docking and crystallization studies validate the hypothesis and confirm the results. The most active compound (t) induces a significant arrest of the cell cycle in G0/G1 phase that ultimately lead to apoptosis, following the mitochondrial pathway, as demonstrated for other choline kinase inhibitors. However additional assays reveal that the inhibition of choline uptake could also be involved in the antiproliferative outcome of this class of compounds. | |||
Synthesis, biological evaluation, in silico modeling and crystallization of novel small monocationic molecules with potent antiproliferative activity by dual mechanism.,Serran-Aguilera L, Mariotto E, Rubbini G, Castro Navas FF, Marco C, Carrasco-Jimenez MP, Ballarotto M, Macchiarulo A, Hurtado-Guerrero R, Viola G, Lopez-Cara LC Eur J Med Chem. 2020 Sep 6;207:112797. doi: 10.1016/j.ejmech.2020.112797. PMID:32977218<ref>PMID:32977218</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7a04" style="background-color:#fffaf0;"></div> | ||
[[Category: Carrasco-Jimenez | |||
[[Category: | ==See Also== | ||
[[Category: Hurtado-Guerrero | *[[Choline kinase 3D structures|Choline kinase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Ballarotto M]] | ||
[[Category: Carrasco-Jimenez MP]] | |||
[[Category: Castro Navas FC]] | |||
[[Category: Hurtado-Guerrero R]] | |||
[[Category: Lopez-Cara LC]] | |||
[[Category: Macchiarulo A]] | |||
[[Category: Marco C]] | |||
[[Category: Mariotto E]] | |||
[[Category: Rubbini G]] | |||
[[Category: Serran-Aguilera L]] | |||
[[Category: Viola G]] | |||
Latest revision as of 15:01, 1 February 2024
Structure of human CKa1 in complex with compound bStructure of human CKa1 in complex with compound b
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 PubMedSeeking for new anticancer drugs with strong antiproliferative activity and simple molecular structure, we designed a novel series of compounds based on our previous reported pharmacophore model composed of five moieties. Antiproliferative assays on four tumoral cell lines and evaluation of Human Choline Kinase CKalpha1 enzymatic activity was performed for these compounds. Among tested molecules, those ones with biphenyl spacer showed betters enzymatic and antiproliferative activities (n-v). Docking and crystallization studies validate the hypothesis and confirm the results. The most active compound (t) induces a significant arrest of the cell cycle in G0/G1 phase that ultimately lead to apoptosis, following the mitochondrial pathway, as demonstrated for other choline kinase inhibitors. However additional assays reveal that the inhibition of choline uptake could also be involved in the antiproliferative outcome of this class of compounds. Synthesis, biological evaluation, in silico modeling and crystallization of novel small monocationic molecules with potent antiproliferative activity by dual mechanism.,Serran-Aguilera L, Mariotto E, Rubbini G, Castro Navas FF, Marco C, Carrasco-Jimenez MP, Ballarotto M, Macchiarulo A, Hurtado-Guerrero R, Viola G, Lopez-Cara LC Eur J Med Chem. 2020 Sep 6;207:112797. doi: 10.1016/j.ejmech.2020.112797. PMID:32977218[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||