4da5 - Revision history

OCA at 10:43, 1 March 2024

OCA — Fri, 01 Mar 2024 10:43:41 GMT

←Older revision		Revision as of 10:43, 1 March 2024
Line 4:		Line 4:
	== 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]] 2.4Å</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®/PubMed®, 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==

OCA at 08:08, 21 September 2022

OCA — Wed, 21 Sep 2022 08:08:39 GMT

←Older revision		Revision as of 08:08, 21 September 2022
Line 1:		Line 1:

	==Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology==		==Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology==
-	<StructureSection load='4da5' size='340' side='right' caption='[[4da5]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='4da5' size='340' side='right'caption='[[4da5]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4da5]] is a 2 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=4DA5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/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"><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='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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHKA, CHK, CKI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [~~http~~://pdbe.org/4da5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4da5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4da5 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:

	==See Also==		==See Also==
-	*[[Choline kinase\|Choline kinase]]	+	*[[Choline kinase 3D structures\|Choline kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Brown, K]]	+	[[Category: Large Structures]]
-	[[Category: Charlton, P]]	+	[[Category: Brown K]]
-	[[Category: Hudson, C]]	+	[[Category: Charlton P]]
-	[[Category: Pollard, J]]	+	[[Category: Hudson C]]
-	~~[[Category: Cytoplasmic]]~~	+	[[Category: Pollard J]]
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Signal transduction]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 02:31, 13 July 2016

OCA — Wed, 13 Jul 2016 02:31:41 GMT

←Older revision		Revision as of 02:31, 13 July 2016
Line 6:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHKA, CHK, CKI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHKA, CHK, CKI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [http://pdbe.org/4da5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [http://www.ebi.ac.uk/pdbsum/4da5 PDBsum]</span></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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [http://pdbe.org/4da5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [http://www.ebi.ac.uk/pdbsum/4da5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4da5 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 15:43, 23 June 2016

OCA — Thu, 23 Jun 2016 15:43:42 GMT

←Older revision		Revision as of 15:43, 23 June 2016
Line 1:		Line 1:
		+
	==Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology==		==Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology==
	<StructureSection load='4da5' size='340' side='right' caption='[[4da5]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='4da5' size='340' side='right' caption='[[4da5]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4da5]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4da5]] is a 2 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=4DA5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA5 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHKA, CHK, CKI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHKA, CHK, CKI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [http://www.ebi.ac.uk/pdbsum/4da5 PDBsum]</span></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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [http://pdbe.org/4da5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [http://www.ebi.ac.uk/pdbsum/4da5 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4da5" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Brown, K]]		[[Category: Brown, K]]
	[[Category: Charlton, P]]		[[Category: Charlton, P]]

OCA at 19:53, 25 December 2014

OCA — Thu, 25 Dec 2014 19:53:42 GMT

←Older revision		Revision as of 19:53, 25 December 2014
Line 7:		Line 7:
	<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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [http://www.ebi.ac.uk/pdbsum/4da5 PDBsum]</span></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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [http://www.ebi.ac.uk/pdbsum/4da5 PDBsum]</span></td></tr>
	</table>		</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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:00, 21 December 2014

OCA — Sun, 21 Dec 2014 10:00:30 GMT

←Older revision		Revision as of 10:00, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4da5\| PDB=4da5 \| SCENE= }}~~	+	==Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology==
-	===Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology===	+	<StructureSection load='4da5' size='340' side='right' caption='[[4da5]], [[Resolution\|resolution]] 2.40Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23416529}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4da5]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA5 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHKA, CHK, CKI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4da5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4da5 RCSB], [http://www.ebi.ac.uk/pdbsum/4da5 PDBsum]</span></td></tr>
		+	</table>
		+	<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.

-	~~==Function==~~	+	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>
-	~~[[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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4da5]] is~~ a ~~2 chain structure with sequence from [http://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].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023416529</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Choline kinase\|Choline kinase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Brown, K.]]	+	[[Category: Brown, K]]
-	[[Category: Charlton, P.]]	+	[[Category: Charlton, P]]
-	[[Category: Hudson, C.]]	+	[[Category: Hudson, C]]
-	[[Category: Pollard, J.]]	+	[[Category: Pollard, J]]
	[[Category: Cytoplasmic]]		[[Category: Cytoplasmic]]
	[[Category: Kinase]]		[[Category: Kinase]]
	[[Category: Signal transduction]]		[[Category: Signal transduction]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:41, 28 August 2013

OCA — Wed, 28 Aug 2013 05:41:05 GMT

←Older revision		Revision as of 05:41, 28 August 2013
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	{{STRUCTURE_4da5\| PDB=4da5 \| SCENE= }}		{{STRUCTURE_4da5\| PDB=4da5 \| SCENE= }}
	===Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology===		===Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology===
		+	{{ABSTRACT_PUBMED_23416529}}

	==Function==		==Function==
Line 9:		Line 10:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:023416529</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Brown, K.]]		[[Category: Brown, K.]]

OCA at 20:31, 17 April 2013

OCA — Wed, 17 Apr 2013 20:31:31 GMT

←Older revision		Revision as of 20:31, 17 April 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4da5\| PDB=4da5 \| SCENE= }}
		+	===Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology===

-	~~The entry 4da5 is ON HOLD~~ ~~until Apr 12 2014~~	+	==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>

-	~~Authors~~: ~~Brown, K~~.~~, Hudson, C~~.~~, Charlton, P~~.~~, Pollard, J~~.	+	==About this Structure==
		+	[[4da5]] is a 2 chain structure with sequence from [http://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].

-	~~Description~~: ~~Choline~~ Kinase ~~alpha acts through a double~~-~~displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and~~ inhibitor ~~kinetics and structural biology~~	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Brown, K.]]
		+	[[Category: Charlton, P.]]
		+	[[Category: Hudson, C.]]
		+	[[Category: Pollard, J.]]
		+	[[Category: Cytoplasmic]]
		+	[[Category: Kinase]]
		+	[[Category: Signal transduction]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 08:42, 2 January 2013

OCA — Wed, 02 Jan 2013 08:42:15 GMT

←Older revision		Revision as of 08:42, 2 January 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4da5 is ON HOLD until ~~Paper Publication~~	+	The entry 4da5 is ON HOLD until Apr 12 2014

	Authors: Brown, K., Hudson, C., Charlton, P., Pollard, J.		Authors: Brown, K., Hudson, C., Charlton, P., Pollard, J.

	Description: Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology		Description: Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology

OCA at 07:25, 18 April 2012

OCA — Wed, 18 Apr 2012 07:25:27 GMT

←Older revision		Revision as of 07:25, 18 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4da5 is ON HOLD	+	The entry 4da5 is ON HOLD until Paper Publication

	Authors: Brown, K., Hudson, C., Charlton, P., Pollard, J.		Authors: Brown, K., Hudson, C., Charlton, P., Pollard, J.

	Description: Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology		Description: Choline Kinase alpha acts through a double-displacement kinetic mechanism involving enzyme isomerisation, as determined through enzyme and inhibitor kinetics and structural biology