Profiling Substrate Promiscuity of Wild-Type Sugar Kinases for Multi-Fluorinated Monosaccharides
| Autor: | Clement Q. Fontenelle, Tessa Keenan, Sabine L. Flitsch, Carl Young, Andrea Marchesi, Bruno Linclau, Alexander Peter Heyam, Martin A. Fascione, Simon J. Charnock, Wendy A. Offen, Kun Huang, Fabio Parmeggiani, Gideon J. Davies, Julien Malassis, Peter Both, Jean-Baptiste Vendeville |
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| Rok vydání: | 2020 |
| Předmět: |
Magnetic Resonance Spectroscopy
Halogenation enzyme discovery Clinical Biochemistry Chemical biology 01 natural sciences Biochemistry Substrate Specificity Galactokinase glycobiology sugar phosphates oligosaccharides Catalytic Domain Drug Discovery Monosaccharide Phosphorylation Molecular Biology Pharmacology chemistry.chemical_classification fluorinated carbohydrates Sugar phosphates biology 010405 organic chemistry Kinase Monosaccharides Phosphotransferases Substrate (chemistry) Active site Fluorine 0104 chemical sciences Kinetics Enzyme kinases chemistry Biocatalysis biology.protein Molecular Medicine |
| ISSN: | 2451-9448 |
| Popis: | Summary 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-fluorogalactose, giving insight into changes in the active site that may account for the specificity of the enzyme toward certain substrate analogs. |
| Databáze: | OpenAIRE |
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