4da5: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4da5]] 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=4DA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DA5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4da5]] 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=4DA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DA5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0H7:(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL[BIS(5-CHLOROTHIOPHEN-2-YL)]METHANOL'>0H7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0H7:(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL[BIS(5-CHLOROTHIOPHEN-2-YL)]METHANOL'>0H7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [https://pdbe.org/4da5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [https://www.ebi.ac.uk/pdbsum/4da5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4da5 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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [https://pdbe.org/4da5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [https://www.ebi.ac.uk/pdbsum/4da5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4da5 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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Choline Kinase is a key component of the Kennedy pathway that converts choline into a number of structural and signalling lipids that are essential for cell growth and survival. One member of the family, Choline Kinase-alpha (ChoKalpha) is frequently up-regulated in human cancers, and expression of ChoKalpha is sufficient to transform cells. Consequently ChoKalpha has been studied as a potential target for therapeutic agents in cancer research. Despite great interest in the enzyme, mechanistic studies have not been reported. In this study, a combination of initial velocity and product inhibition studies, together with the kinetic and structural characterisation of a novel ChoKalpha inhibitor is used to support a mechanism of action for human ChoKalpha. Substrate and inhibition kinetics are consistent with an iso double displacement mechanism, in which the gamma-phosphate from ATP is transferred to choline in two distinct steps via a phospho-enzyme intermediate. Co-crystal structures, and existing site-specific mutation studies, support an important role for Asp306, in stabilising the phospho-enzyme intermediate. The kinetics also indicate a distinct kinetic (isomerisation) step associated with product release, which may be attributed to a conformational change in the protein to disrupt an interaction between Asp306 and the phosphocholine product, facilitating product release. This study describes a mechanism for ChoKalpha that is unusual amongst kinases, and highlights the availability of different enzyme states that can be exploited for drug discovery.
 
Kinetic and mechanistic characterisation of Choline Kinase-alpha.,Hudson CS, Knegtel RM, Brown K, Charlton PA, Pollard JR Biochim Biophys Acta. 2013 Jun;1834(6):1107-16. doi:, 10.1016/j.bbapap.2013.02.008. Epub 2013 Feb 13. PMID:23416529<ref>PMID:23416529</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4da5" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Retrieved from "https://proteopedia.org/4da5"