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

Aysha B. Mezoughi, Chiara Costanzo, Gregor M. Parker, Enas M. Behiry, Alan Scott, Andrew C. Wood, Sarah E. Adams, Richard B. Sessions, Joel Loveridge Orcid Logo

Molecules, Volume: 26, Issue: 14, Start page: 4189

Swansea University Authors: Chiara Costanzo, Joel Loveridge Orcid Logo

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DOI (Published version): 10.3390/molecules26144189

Abstract

Lytic transglycosylases such as Slt35 from E. coli 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 glycosi...

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Published in: Molecules
ISSN: 1420-3049
Published: MDPI AG 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa57288
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spelling 2022-07-08T12:46:41.0361165 v2 57288 2021-07-09 The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli 3a4a7acaa2c9e9b0bb8e0e22052310a7 Chiara Costanzo Chiara Costanzo true false 5dd2760b388ec3cc2af33bb62f3f151a 0000-0002-8528-4019 Joel Loveridge Joel Loveridge true false 2021-07-09 CHEM Lytic transglycosylases such as Slt35 from E. coli 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. IC50 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 E. coli. Journal Article Molecules 26 14 4189 MDPI AG 1420-3049 lytic transglycosylase; thionine acetate; enzyme inhibition; antibacterial 9 7 2021 2021-07-09 10.3390/molecules26144189 Data are contained within the article or Supplementary Materials. COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University External research funder(s) paid the OA fee (includes OA grants disbursed by the Library) This research was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC), grant number BB/L01758X/1; the Life Sciences Research Network Wales, grant number NRNRG4Mar039; the Libyan Embassy (London), PhD studentship 10007 to A.B.A.M.; the Royal Society of Chemistry, Undergraduate Research Bursary to G.M.P.; Cardiff University and Swansea University. The APC was funded by Swansea University. BB/L01758X/1; NRNRG4Mar039; 2022-07-08T12:46:41.0361165 2021-07-09T14:43:30.0293689 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Aysha B. Mezoughi 1 Chiara Costanzo 2 Gregor M. Parker 3 Enas M. Behiry 4 Alan Scott 5 Andrew C. Wood 6 Sarah E. Adams 7 Richard B. Sessions 8 Joel Loveridge 0000-0002-8528-4019 9 57288__20516__a5b817b615944eca8c1a60cba6ecfd21.pdf 57288.pdf 2021-08-02T15:34:58.3933920 Output 3601659 application/pdf Version of Record true © 2021 by the authors.This is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license true eng https://creativecommons.org/licenses/by/4.0/
title The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli
spellingShingle The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli
Chiara Costanzo
Joel Loveridge
title_short The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli
title_full The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli
title_fullStr The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli
title_full_unstemmed The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli
title_sort The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli
author_id_str_mv 3a4a7acaa2c9e9b0bb8e0e22052310a7
5dd2760b388ec3cc2af33bb62f3f151a
author_id_fullname_str_mv 3a4a7acaa2c9e9b0bb8e0e22052310a7_***_Chiara Costanzo
5dd2760b388ec3cc2af33bb62f3f151a_***_Joel Loveridge
author Chiara Costanzo
Joel Loveridge
author2 Aysha B. Mezoughi
Chiara Costanzo
Gregor M. Parker
Enas M. Behiry
Alan Scott
Andrew C. Wood
Sarah E. Adams
Richard B. Sessions
Joel Loveridge
format Journal article
container_title Molecules
container_volume 26
container_issue 14
container_start_page 4189
publishDate 2021
institution Swansea University
issn 1420-3049
doi_str_mv 10.3390/molecules26144189
publisher MDPI AG
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
document_store_str 1
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description Lytic transglycosylases such as Slt35 from E. coli 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. IC50 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 E. coli.
published_date 2021-07-09T04:12:55Z
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