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== | ==Crystal structure of Human Choline Kinase alpha-2 in complex with ADP== | ||
Choline kinase, responsible for the phosphorylation of choline to | <StructureSection load='2ckp' size='340' side='right'caption='[[2ckp]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ckp]] 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=2CKP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CKP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</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></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=2ckp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ckp OCA], [https://pdbe.org/2ckp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ckp RCSB], [https://www.ebi.ac.uk/pdbsum/2ckp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ckp ProSAT]</span></td></tr> | |||
</table> | |||
== 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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ck/2ckp_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ckp ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:17007874</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 2ckp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Choline kinase|Choline kinase]] | |||
*[[Choline kinase 3D structures|Choline kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Lavie | [[Category: Lavie A]] | ||
[[Category: Malito | [[Category: Malito E]] | ||
Latest revision as of 17:19, 13 December 2023
Crystal structure of Human Choline Kinase alpha-2 in complex with ADPCrystal structure of Human Choline Kinase alpha-2 in complex with ADP
Structural highlights
FunctionCHKA_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 PubMedCholine 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 AlsoReferences
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