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| | <StructureSection load='2cko' size='340' side='right'caption='[[2cko]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='2cko' size='340' side='right'caption='[[2cko]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cko]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CKO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cko]] 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=2CKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CKO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</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]] 2.15Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ckp|2ckp]], [[2ckq|2ckq]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Choline_kinase Choline kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.32 2.7.1.32] </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=2cko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cko OCA], [https://pdbe.org/2cko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cko RCSB], [https://www.ebi.ac.uk/pdbsum/2cko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cko 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=2cko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cko OCA], [https://pdbe.org/2cko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cko RCSB], [https://www.ebi.ac.uk/pdbsum/2cko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cko 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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Choline kinase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lavie, A]] | + | [[Category: Lavie A]] |
| - | [[Category: Malito, E]] | + | [[Category: Malito E]] |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Phosphatydilcholine]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Choline kinase, responsible for the phosphorylation of choline to phosphocholine as the first step of the CDP-choline pathway for the biosynthesis of phosphatidylcholine, has been recognized as a new target for anticancer therapy. Crystal structures of human choline kinase in its apo, ADP and phosphocholine-bound complexes, respectively, reveal the molecular details of the substrate binding sites. ATP binds in a cavity where residues from both the N and C-terminal lobes contribute to form a cleft, while the choline-binding site constitutes a deep hydrophobic groove in the C-terminal domain with a rim composed of negatively charged residues. Upon binding of choline, the enzyme undergoes conformational changes independently affecting the N-terminal domain and the ATP-binding loop. From this structural analysis and comparison with other kinases, and from mutagenesis data on the homologous Caenorhabditis elegans choline kinase, a model of the ternary ADP.phosphocholine complex was built that reveals the molecular basis for the phosphoryl transfer activity of this enzyme.
Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine.,Malito E, Sekulic N, Too WC, Konrad M, Lavie A J Mol Biol. 2006 Nov 24;364(2):136-51. Epub 2006 Sep 3. PMID:17007874[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Malito E, Sekulic N, Too WC, Konrad M, Lavie A. Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine. J Mol Biol. 2006 Nov 24;364(2):136-51. Epub 2006 Sep 3. PMID:17007874 doi:10.1016/j.jmb.2006.08.084
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