4cg8

From Proteopedia

(Difference between revisions)

Current revision

Human choline kinase a1 in complex with compound 14

Structural highlights

4cg8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.75Å
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

Human 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.

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
↑ 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. Discovery of a New Binding Site on Human Choline Kinase alpha1: Design, Synthesis, Crystallographic Studies, and Biological Evaluation of Asymmetrical Bispyridinium Derivatives. J Med Chem. 2014 Jan 14. PMID:24387243 doi:http://dx.doi.org/10.1021/jm401665x

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/4cg8"

@@ Line 3: / Line 3: @@
 <StructureSection load='4cg8' size='340' side='right'caption='[[4cg8]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4cg8]] 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=4CG8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CG8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4cg8]] 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=4CG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CG8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=G8S:4-[(4-CHLOROPHENYL)(METHYL)AMINO]-1-{4-[4-(4-{[4-(DIMETHYLAMINO)PYRIDINIUM-1-YL]METHYL}PHENYL)BUTYL]BENZYL}PYRIDINIUM'>G8S</scene>, <scene name='pdbligand=G8V:1-BENZYL-4-(DIMETHYLAMINO)PYRIDINIUM'>G8V</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cg9|4cg9]], [[4cga|4cga]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G8S:4-[(4-CHLOROPHENYL)(METHYL)AMINO]-1-{4-[4-(4-{[4-(DIMETHYLAMINO)PYRIDINIUM-1-YL]METHYL}PHENYL)BUTYL]BENZYL}PYRIDINIUM'>G8S</scene>, <scene name='pdbligand=G8V:1-BENZYL-4-(DIMETHYLAMINO)PYRIDINIUM'>G8V</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=4cg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cg8 OCA], [http://pdbe.org/4cg8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cg8 RCSB], [http://www.ebi.ac.uk/pdbsum/4cg8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cg8 ProSAT]</span></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=4cg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cg8 OCA], [https://pdbe.org/4cg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cg8 RCSB], [https://www.ebi.ac.uk/pdbsum/4cg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cg8 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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 ==
@@ Line 21: / Line 21: @@
 ==See Also==
-*[[Choline kinase|Choline kinase]]
+*[[Choline kinase 3D structures|Choline kinase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Conejo-Garcia, A]]
+[[Category: Conejo-Garcia A]]
-[[Category: Entrena-Guadix, A]]
+[[Category: Entrena-Guadix A]]
-[[Category: Figuerola-Conchas, A]]
+[[Category: Figuerola-Conchas A]]
-[[Category: Hurtado-Guerrero, R]]
+[[Category: Hurtado-Guerrero R]]
-[[Category: Rubio-Ruiz, B]]
+[[Category: Rubio-Ruiz B]]
-[[Category: Cancer]]
-[[Category: Drug target]]
-[[Category: Transferase]]

4cg8

From Proteopedia

Current revision

Human choline kinase a1 in complex with compound 14

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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