Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides
Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides
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-2fluoro galactose, giving insight into changes in the active site that may account for the specificity of the enzyme towards certain substrate analogues.
biocatalysis, kinases, sugar phosphates, fluorinated carbohydrates, oligosaccharides, glycobiology, enzyme discovery
1199-1206.e5
Keenan, Tessa
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Parmeggiani, Fabio
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Malassis, Julien GJ
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Fontenelle, Clement Q
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Vendeville, Jean B
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Offen, Wendy
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Both, Peter
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Huang, Kun
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Marchesi, Andrea
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Heyam, Alex
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Young, Carl
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Charnock, Simon J.
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Davies, Gideon J.
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Linclau, Bruno
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Flitsch, Sabine L.
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Fascione, Martin A.
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17 September 2020
Keenan, Tessa
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Parmeggiani, Fabio
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Malassis, Julien GJ
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Fontenelle, Clement Q
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Vendeville, Jean B
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Offen, Wendy
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Both, Peter
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Huang, Kun
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Marchesi, Andrea
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Heyam, Alex
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Young, Carl
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Charnock, Simon J.
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Davies, Gideon J.
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Linclau, Bruno
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Flitsch, Sabine L.
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Fascione, Martin A.
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Keenan, Tessa, Parmeggiani, Fabio, Malassis, Julien GJ, Fontenelle, Clement Q, Vendeville, Jean B, Offen, Wendy, Both, Peter, Huang, Kun, Marchesi, Andrea, Heyam, Alex, Young, Carl, Charnock, Simon J., Davies, Gideon J., Linclau, Bruno, Flitsch, Sabine L. and Fascione, Martin A.
(2020)
Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides.
Cell Chemical Biology, 27 (9), .
(doi:10.1016/j.chembiol.2020.06.005).
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-2fluoro galactose, giving insight into changes in the active site that may account for the specificity of the enzyme towards certain substrate analogues.
Text
MAF_Kinases paper - _Cell_Chem_Biol_postprint
- Accepted Manuscript
More information
Accepted/In Press date: 12 June 2020
e-pub ahead of print date: 2 July 2020
Published date: 17 September 2020
Keywords:
biocatalysis, kinases, sugar phosphates, fluorinated carbohydrates, oligosaccharides, glycobiology, enzyme discovery
Identifiers
Local EPrints ID: 450595
URI: http://eprints.soton.ac.uk/id/eprint/450595
ISSN: 2451-9448
PURE UUID: 6b94184e-3493-494b-9492-654c51742508
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Date deposited: 04 Aug 2021 16:35
Last modified: 17 Mar 2024 05:40
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Contributors
Author:
Tessa Keenan
Author:
Fabio Parmeggiani
Author:
Julien GJ Malassis
Author:
Clement Q Fontenelle
Author:
Jean B Vendeville
Author:
Wendy Offen
Author:
Peter Both
Author:
Kun Huang
Author:
Andrea Marchesi
Author:
Alex Heyam
Author:
Carl Young
Author:
Simon J. Charnock
Author:
Gideon J. Davies
Author:
Sabine L. Flitsch
Author:
Martin A. Fascione
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