7nb2

Crystal structure of human choline alpha in complex with an inhibitor

spinqualitylabelsall models 7nb2, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nb2 is a 2 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 2.4Å Ligands: EPE, MG, U6E Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Choline kinase 3D structures

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