The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>

Lytic transglycosylases such as Slt35 from <i>E. coli</i> are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit S...

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Main Authors: Aysha B. Mezoughi, Chiara M. Costanzo, Gregor M. Parker, Enas M. Behiry, Alan Scott, Andrew C. Wood, Sarah E. Adams, Richard B. Sessions, E. Joel Loveridge
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/26/14/4189
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author Aysha B. Mezoughi
Chiara M. Costanzo
Gregor M. Parker
Enas M. Behiry
Alan Scott
Andrew C. Wood
Sarah E. Adams
Richard B. Sessions
E. Joel Loveridge
author_facet Aysha B. Mezoughi
Chiara M. Costanzo
Gregor M. Parker
Enas M. Behiry
Alan Scott
Andrew C. Wood
Sarah E. Adams
Richard B. Sessions
E. Joel Loveridge
author_sort Aysha B. Mezoughi
collection DOAJ
description Lytic transglycosylases such as Slt35 from <i>E. coli</i> are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit Slt35. While glycosidase inhibitors such as 1-deoxynojirimycin, castanospermine, thiamet G and miglitol had no effect, the phenothiazinium dye thionine acetate was found to be a weak inhibitor. IC<sub>50</sub> values and binding constants for thionine acetate were similar for Slt35 and the hen egg white lysozyme. Molecular docking simulations suggest that thionine binds to the active site of both Slt35 and lysozyme, although it does not make direct interactions with the side-chain of the catalytic Asp and Glu residues as might be expected based on other inhibitors. Thionine acetate also increased the potency of the beta-lactam antibiotic ampicillin against a laboratory strain of <i>E. coli</i>.
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spelling doaj.art-84b975e7244748d283e024c32655050f2023-11-22T04:29:56ZengMDPI AGMolecules1420-30492021-07-012614418910.3390/molecules26144189The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>Aysha B. Mezoughi0Chiara M. Costanzo1Gregor M. Parker2Enas M. Behiry3Alan Scott4Andrew C. Wood5Sarah E. Adams6Richard B. Sessions7E. Joel Loveridge8School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKDepartment of Chemistry, Swansea University, Singleton Park, Swansea SA2 8PP, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKLytic transglycosylases such as Slt35 from <i>E. coli</i> are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit Slt35. While glycosidase inhibitors such as 1-deoxynojirimycin, castanospermine, thiamet G and miglitol had no effect, the phenothiazinium dye thionine acetate was found to be a weak inhibitor. IC<sub>50</sub> values and binding constants for thionine acetate were similar for Slt35 and the hen egg white lysozyme. Molecular docking simulations suggest that thionine binds to the active site of both Slt35 and lysozyme, although it does not make direct interactions with the side-chain of the catalytic Asp and Glu residues as might be expected based on other inhibitors. Thionine acetate also increased the potency of the beta-lactam antibiotic ampicillin against a laboratory strain of <i>E. coli</i>.https://www.mdpi.com/1420-3049/26/14/4189lytic transglycosylasethionine acetateenzyme inhibitionantibacterial
spellingShingle Aysha B. Mezoughi
Chiara M. Costanzo
Gregor M. Parker
Enas M. Behiry
Alan Scott
Andrew C. Wood
Sarah E. Adams
Richard B. Sessions
E. Joel Loveridge
The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
Molecules
lytic transglycosylase
thionine acetate
enzyme inhibition
antibacterial
title The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_full The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_fullStr The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_full_unstemmed The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_short The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_sort lysozyme inhibitor thionine acetate is also an inhibitor of the soluble lytic transglycosylase slt35 from i escherichia coli i
topic lytic transglycosylase
thionine acetate
enzyme inhibition
antibacterial
url https://www.mdpi.com/1420-3049/26/14/4189
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