5sca | pdb_00005sca

Structure of liver pyruvate kinase in complex with anthraquinone derivative 36

spinqualitylabelsall models 5sca, resolution 1.92Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5sca is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FBP, I7N, K, MG, OXL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP production during liver cell glycolysis and is considered a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). In this study, we report the first ADP-competitive PKL inhibitors and identify several starting points for the further optimization of these inhibitors. Modeling and structural biology guided the optimization of a PKL-specific anthraquinone-based compound. A structure-activity relationship study of 47 novel synthetic derivatives revealed PKL inhibitors with half-maximal inhibitory concentration (IC50) values in the 200 nM range. Despite the difficulty involved in studying a binding site as exposed as the ADP site, these derivatives feature expanded structural diversity and chemical spaces that may be used to improve their inhibitory activities against PKL. The obtained results expand the knowledge of the structural requirements for interactions with the ADP-binding site of PKL. Anthraquinone derivatives as ADP-competitive inhibitors of liver pyruvate kinase.,Nain-Perez A, Foller Fuchtbauer A, Haversen L, Lulla A, Gao C, Matic J, Monjas L, Rodriguez A, Brear P, Kim W, Hyvonen M, Boren J, Mardinoglu A, Uhlen M, Grotli M Eur J Med Chem. 2022 Mar 8;234:114270. doi: 10.1016/j.ejmech.2022.114270. PMID:35290845 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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