7nb3: Difference between revisions
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==Crystal structure of human choline alpha in complex with an inhibitor== | ==Crystal structure of human choline alpha in complex with an inhibitor== | ||
<StructureSection load='7nb3' size='340' side='right'caption='[[7nb3]]' scene=''> | <StructureSection load='7nb3' size='340' side='right'caption='[[7nb3]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NB3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7nb3]] 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=7NB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NB3 FirstGlance]. <br> | ||
</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=7nb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nb3 OCA], [https://pdbe.org/7nb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nb3 RCSB], [https://www.ebi.ac.uk/pdbsum/7nb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nb3 ProSAT]</span></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]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=U6H:4-(6-azanyl-2-pyridin-4-yl-purin-9-yl)-~{N}-(3-methoxyphenyl)cyclohexane-1-carboxamide'>U6H</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=7nb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nb3 OCA], [https://pdbe.org/7nb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nb3 RCSB], [https://www.ebi.ac.uk/pdbsum/7nb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nb3 ProSAT]</span></td></tr> | |||
</table> | </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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In this article we describe the identification of unprecedented ATP-competitive ChoKalpha inhibitors starting from initial hit NMS-P830 that binds to ChoKalpha in an ATP concentration-dependent manner. This result is confirmed by the co-crystal structure of NMS-P830 in complex with Delta75-ChoKalpha. NMS-P830 is able to inhibit ChoKalpha in cells resulting in the reduction of intracellular phosphocholine formation. A structure-based medicinal chemistry program resulted in the identification of selective compounds that have good biochemical activity, solubility and metabolic stability and are suitable for further optimization. The ChoKalpha inhibitors disclosed in this article demonstrate for the first time the possibility to inhibit ChoKalpha with ATP-competitive compounds. | |||
Identification of unprecedented ATP-competitive choline kinase inhibitors.,Quartieri F, Nesi M, Avanzi NR, Borghi D, Casale E, Corti E, Cucchi U, Donati D, Fasolini M, Felder ER, Galvani A, Giorgini ML, Lomolino A, Menichincheri M, Orrenius C, Perrera C, Re Depaolini S, Riccardi-Sirtori F, Salsi E, Isacchi A, Gnocchi P Bioorg Med Chem Lett. 2021 Aug 18;51:128310. doi: 10.1016/j.bmcl.2021.128310. PMID:34416377<ref>PMID:34416377</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7nb3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Choline kinase 3D structures|Choline kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Casale E]] | [[Category: Casale E]] | ||
[[Category: Fasolini M]] | [[Category: Fasolini M]] | ||
Latest revision as of 15:32, 1 February 2024
Crystal structure of human choline alpha in complex with an inhibitorCrystal structure of human choline alpha in complex with an inhibitor
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] Publication Abstract from PubMedIn this article we describe the identification of unprecedented ATP-competitive ChoKalpha inhibitors starting from initial hit NMS-P830 that binds to ChoKalpha in an ATP concentration-dependent manner. This result is confirmed by the co-crystal structure of NMS-P830 in complex with Delta75-ChoKalpha. NMS-P830 is able to inhibit ChoKalpha in cells resulting in the reduction of intracellular phosphocholine formation. A structure-based medicinal chemistry program resulted in the identification of selective compounds that have good biochemical activity, solubility and metabolic stability and are suitable for further optimization. The ChoKalpha inhibitors disclosed in this article demonstrate for the first time the possibility to inhibit ChoKalpha with ATP-competitive compounds. Identification of unprecedented ATP-competitive choline kinase inhibitors.,Quartieri F, Nesi M, Avanzi NR, Borghi D, Casale E, Corti E, Cucchi U, Donati D, Fasolini M, Felder ER, Galvani A, Giorgini ML, Lomolino A, Menichincheri M, Orrenius C, Perrera C, Re Depaolini S, Riccardi-Sirtori F, Salsi E, Isacchi A, Gnocchi P Bioorg Med Chem Lett. 2021 Aug 18;51:128310. doi: 10.1016/j.bmcl.2021.128310. PMID:34416377[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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