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| | <StructureSection load='3feg' size='340' side='right'caption='[[3feg]], [[Resolution|resolution]] 1.30Å' scene=''> | | <StructureSection load='3feg' size='340' side='right'caption='[[3feg]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3feg]] 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=3FEG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3FEG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3feg]] 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=3FEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FEG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=HC7:(2S)-2-[4-({DIMETHYL[2-(PHOSPHONOOXY)ETHYL]AMMONIO}ACETYL)BIPHENYL-4-YL]-2-HYDROXY-4,4-DIMETHYLMORPHOLIN-4-IUM'>HC7</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 1.302Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHKB, CHETK, CHKL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=HC7:(2S)-2-[4-({DIMETHYL[2-(PHOSPHONOOXY)ETHYL]AMMONIO}ACETYL)BIPHENYL-4-YL]-2-HYDROXY-4,4-DIMETHYLMORPHOLIN-4-IUM'>HC7</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3feg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3feg OCA], [http://pdbe.org/3feg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3feg RCSB], [http://www.ebi.ac.uk/pdbsum/3feg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3feg 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=3feg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3feg OCA], [https://pdbe.org/3feg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3feg RCSB], [https://www.ebi.ac.uk/pdbsum/3feg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3feg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CHKB_HUMAN CHKB_HUMAN]] Has a key role in phospholipid biosynthesis. Catalyzes the first step in phosphatidylethanolamine biosynthesis. Phosphorylates ethanolamine, and can also act on choline (in vitro). Has higher activity with ethanolamine. May not significantly contribute to in vivo phosphatidylcholine biosynthesis.<ref>PMID:19915674</ref> | + | [https://www.uniprot.org/uniprot/CHKB_HUMAN CHKB_HUMAN] Has a key role in phospholipid biosynthesis. Catalyzes the first step in phosphatidylethanolamine biosynthesis. Phosphorylates ethanolamine, and can also act on choline (in vitro). Has higher activity with ethanolamine. May not significantly contribute to in vivo phosphatidylcholine biosynthesis.<ref>PMID:19915674</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bountra C]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Edwards AM]] |
| - | [[Category: Hong, B S]] | + | [[Category: Hong BS]] |
| - | [[Category: MacKenzie, F]] | + | [[Category: MacKenzie F]] |
| - | [[Category: Park, H W]] | + | [[Category: Park HW]] |
| - | [[Category: Rabeh, W M]] | + | [[Category: Rabeh WM]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Tempel W]] |
| - | [[Category: Tempel, W]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | |
| - | [[Category: Choline kinase]]
| + | |
| - | [[Category: Hemicholinium-3]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Non-protein kinase]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
3feg 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 1.302Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CHKB_HUMAN Has a key role in phospholipid biosynthesis. Catalyzes the first step in phosphatidylethanolamine biosynthesis. Phosphorylates ethanolamine, and can also act on choline (in vitro). Has higher activity with ethanolamine. May not significantly contribute to in vivo phosphatidylcholine biosynthesis.[1]
Publication Abstract from PubMed
Human choline kinase (ChoK) catalyzes the first reaction in phosphatidylcholine biosynthesis and exists as ChoKalpha (alpha1 and alpha2) and ChoKbeta isoforms. Recent studies suggest that ChoK is implicated in tumorigenesis and emerging as an attractive target for anticancer chemotherapy. To extend our understanding of the molecular mechanism of ChoK inhibition, we have determined the high resolution x-ray structures of the ChoKalpha1 and ChoKbeta isoforms in complex with hemicholinium-3 (HC-3), a known inhibitor of ChoK. In both structures, HC-3 bound at the conserved hydrophobic groove on the C-terminal lobe. One of the HC-3 oxazinium rings complexed with ChoKalpha1 occupied the choline-binding pocket, providing a structural explanation for its inhibitory action. Interestingly, the HC-3 molecule co-crystallized with ChoKbeta was phosphorylated in the choline binding site. This phosphorylation, albeit occurring at a very slow rate, was confirmed experimentally by mass spectroscopy and radioactive assays. Detailed kinetic studies revealed that HC-3 is a much more potent inhibitor for ChoKalpha isoforms (alpha1 and alpha2) compared with ChoKbeta. Mutational studies based on the structures of both inhibitor-bound ChoK complexes demonstrated that Leu-401 of ChoKalpha2 (equivalent to Leu-419 of ChoKalpha1), or the corresponding residue Phe-352 of ChoKbeta, which is one of the hydrophobic residues neighboring the active site, influences the plasticity of the HC-3-binding groove, thereby playing a key role in HC-3 sensitivity and phosphorylation.
Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: single amino acid near the active site influences inhibitor sensitivity.,Hong BS, Allali-Hassani A, Tempel W, Finerty PJ Jr, Mackenzie F, Dimov S, Vedadi M, Park HW J Biol Chem. 2010 May 21;285(21):16330-40. Epub 2010 Mar 18. PMID:20299452[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
- ↑ Hong BS, Allali-Hassani A, Tempel W, Finerty PJ Jr, Mackenzie F, Dimov S, Vedadi M, Park HW. Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: single amino acid near the active site influences inhibitor sensitivity. J Biol Chem. 2010 May 21;285(21):16330-40. Epub 2010 Mar 18. PMID:20299452 doi:10.1074/jbc.M109.039024
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