Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides

Tessa Keenan, Fabio Parmeggiani, Julien Malassis, Clement Fontenelle, Jean-Baptiste Vendeville, Wendy Anne Offen, Peter Both, Kun Huang, Andrea Marchesi, Alexander Peter Heyam, Carl Young, Simon J. Charnock, Gideon John Davies, Bruno Linclau, Sabine L. Flitsch, Martin Anthony Fascione

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Fluorinated sugar-1-phosphates are of emerging importance as intermediates in the chemical and biocatalytic synthesis of modified oligosaccharides, as well as probes for chemical biology. Here we present a systematic study of the activity of a wide range of anomeric sugar kinases (galacto- and N-acetylhexosamine kinases) against a panel of fluorinated monosaccharides, leading to the first examples of polyfluorinated substrates accepted by this class of enzymes. We have discovered four new N-acetylhexosamine kinases with a different substrate scope, thus expanding the number of homologs available in this subclass of kinases. Lastly, we have solved the crystal structure of a galactokinase in complex with 2-deoxy-2-fluoro galactose, giving insight into changes in the active site that may account for the specificity of the enzyme towards certain substrate analogues.
Original languageEnglish
JournalCell Chemical Biology
Early online date2 Jul 2020
Publication statusE-pub ahead of print - 2 Jul 2020

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