The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli |
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| 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 |
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| Affiliation: | 1.School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK; (A.B.M.); (G.M.P.); (E.M.B.); (A.S.); (A.C.W.); (S.E.A.);2.Department of Chemistry, Swansea University, Singleton Park, Swansea SA2 8PP, UK;3.School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK; |
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| 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 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. |
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| Keywords: | lytic transglycosylase thionine acetate enzyme inhibition antibacterial |
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