8OME
Crystal structure of hKHK-A in complex with compound-4
8OME の概要
エントリーDOI | 10.2210/pdb8ome/pdb |
分子名称 | Ketohexokinase, compound (3 entities in total) |
機能のキーワード | ketohexokinase, khk, inhibitor bound, sugar kinase, isoform selectivity, sugar binding protein |
由来する生物種 | Homo sapiens (human) |
タンパク質・核酸の鎖数 | 4 |
化学式量合計 | 133019.61 |
構造登録者 | |
主引用文献 | Ebenhoch, R.,Bauer, M.,Romig, H.,Gottschling, D.,Kley, J.T.,Heine, N.,Weber, A.,Uphues, I.,Nar, H.,Pautsch, A. Crystal structures of human and mouse ketohexokinase provide a structural basis for species- and isoform-selective inhibitor design. Acta Crystallogr D Struct Biol, 79:871-880, 2023 Cited by PubMed Abstract: A molecular understanding of the proteins involved in fructose metabolism is essential for controlling the current spread of fructose-related obesity, diabetes and related adverse metabolic states in Western populations. Fructose catabolism starts with the phosphorylation of D-fructose to fructose 1-phosphate by ketohexokinase (KHK). KHK exists in two alternatively spliced isoforms: the hepatic and intestinal isoform KHK-C and the peripheral isoform KHK-A. Here, the structure of apo murine KHK (mKHK), which differs from structures of human KHK in overall conformation, is reported. An isoform-selective ligand, which offers a 50-fold higher potency on mKHK and human KHK-A compared with KHK-C, is further characterized. In mKHK, large-scale conformational changes are observed upon ligand binding. The structures suggest a combined strategy for the design of species- and isoform-selective KHK inhibitors. PubMed: 37712434DOI: 10.1107/S2059798323006137 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2 Å) |
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