The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from
Autor: | 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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Rok vydání: | 2021 |
Předmět: |
Models
Molecular Binding Sites Protein Conformation Escherichia coli Proteins Glycosyltransferases Peptidoglycan Acetates Crystallography X-Ray Article Molecular Docking Simulation antibacterial Bacterial Proteins Cell Wall Phenothiazines Catalytic Domain Escherichia coli thionine acetate Muramidase lytic transglycosylase Amino Acid Sequence enzyme inhibition |
Zdroj: | Molecules |
ISSN: | 1420-3049 |
Popis: | 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. |
Databáze: | OpenAIRE |
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