8OMF

Crystal structure of hKHK-C in complex with compound-4

Summary for 8OMF

• Entry DOI: 10.2210/pdb8omf/pdb
• Descriptor: Ketohexokinase, SULFATE ION, compound, ... (4 entities in total)
• Functional Keywords: ketohexokinase, khk, sugar kinase, species selectivity, isoform selectivity, inhibited, sugar binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 69510.67

Authors

Ebenhoch, R.,Pautsch, A. (deposition date: 2023-03-31, release date: 2023-09-27, Last modification date: 2023-10-18)

Primary citation

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

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: 37712434
DOI: 10.1107/S2059798323006137

Experimental method

X-RAY DIFFRACTION (2.14 Å)