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Profiling substrate promiscuity of wild-type sugar kinases for multi-fluorinated monosaccharides

DOI: 10.1016/j.chembiol.2020.06.005 DOI Help

Authors: Tessa Keenan (University of York) , Fabio Parmeggiani (University of Manchester) , Julien Malassis (University of Southampton) , Clement Q. Fontenelle (University of Southampton) , Jean-Baptiste Vendeville (University of Southampton) , Wendy Offen (University of York) , Peter Both (University of Manchester) , Kun Huang (University of Manchester) , Andrea Marchesi (University of Manchester) , Alex Heyam (University of York) , Carl Young (Prozomix Limited) , Simon J. Charnock (Prozomix Limited) , Gideon J. Davies (The University of York) , Bruno Linclau (University of Southampton) , Sabine L. Flitsch (University of Manchester) , Martin A. Fascione (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Chemical Biology

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 13587 , 18598

Abstract: 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.

Journal Keywords: biocatalysis; kinases; sugar phosphates; fluorinated carbohydrates; oligosaccharides; glycobiology; enzyme discovery

Diamond Keywords: Enzymes

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 14/07/2020 11:40

Discipline Tags:

Catalysis Life Sciences & Biotech Structural biology Chemistry Biochemistry

Technical Tags:

Diffraction Macromolecular Crystallography (MX)