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

doi:10.1016/j.chembiol.2020.06.005

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

Research output: Contribution to journal › Article › peer-review

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-fluoro galactose, giving insight into changes in the active site that may account for the specificity of the enzyme towards certain substrate analogues.

Original language	English
Journal	Cell Chemical Biology
Early online date	2 Jul 2020
DOIs	https://doi.org/10.1016/j.chembiol.2020.06.005
Publication status	E-pub ahead of print - 2 Jul 2020

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This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

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10.1016/j.chembiol.2020.06.005

MAF_Kinases paper - _Cell_Chem_Biol_postprint
This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.
Accepted author manuscript, 902 KB

Chemo-enzymatic Production of Specialty Glycans
Fascione, M. A. (Principal investigator)
19/10/15 → 18/10/20
Project: Research project (funded) › Research

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Keenan, T., Parmeggiani, F., Malassis, J., Fontenelle, C., Vendeville, J.-B., Offen, W. A., Both, P., Huang, K., Marchesi, A., Heyam, A. P., Young, C., Charnock, S. J., Davies, G. J., Linclau, B., Flitsch, S. L., & Fascione, M. A. (2020). Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides. Cell Chemical Biology. Advance online publication. https://doi.org/10.1016/j.chembiol.2020.06.005

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title = "Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides",

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-fluoro galactose, giving insight into changes in the active site that may account for the specificity of the enzyme towards certain substrate analogues.",

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

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Keenan, T, Parmeggiani, F, Malassis, J, Fontenelle, C, Vendeville, J-B, Offen, WA, Both, P, Huang, K, Marchesi, A, Heyam, AP, Young, C, Charnock, SJ, Davies, GJ, Linclau, B, Flitsch, SL & Fascione, MA 2020, 'Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides', Cell Chemical Biology. https://doi.org/10.1016/j.chembiol.2020.06.005

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T1 - Profiling substrate promiscuity of wild-type sugar kinases for multifluorinated monosaccharides

AU - Keenan, Tessa

AU - Parmeggiani, Fabio

AU - Malassis, Julien

AU - Fontenelle, Clement

AU - Vendeville, Jean-Baptiste

AU - Offen, Wendy Anne

AU - Both, Peter

AU - Huang, Kun

AU - Marchesi, Andrea

AU - Heyam, Alexander Peter

AU - Young, Carl

AU - Charnock, Simon J.

AU - Davies, Gideon John

AU - Linclau, Bruno

AU - Flitsch, Sabine L.

AU - Fascione, Martin Anthony

N1 - This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2020/7/2

Y1 - 2020/7/2

N2 - 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.

AB - 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.

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DO - 10.1016/j.chembiol.2020.06.005

M3 - Article

SN - 2451-9448

JO - Cell Chemical Biology

JF - Cell Chemical Biology

ER -

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

Abstract

Bibliographical note

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Projects

Chemo-enzymatic Production of Specialty Glycans

Cite this