Unraveling the Compositional and Molecular Features Involved in Lysozyme-Benzothiazole Derivative Interactions

Abstract

In this work we present a computational analysis together with experimental studies, focusing on the interaction between a benzothiazole (BTS) and lysozyme. Results obtained from isothermal titration calorimetry, UV-vis, and fluorescence were contrasted and complemented with molecular docking and machine learning techniques. The free energy values obtained both experimentally and theoretically showed excellent similarity. Calorimetry, UV-vis, and 3D/2D-lig-plot analysis revealed that the most relevant interactions between BTS and lysozyme are based on a predominance of aromatic, hydrophobic Van der Waals interactions, mainly aromatic edge-to-face (T-shaped) π-π stacking interactions between the benzene ring belonging to the 2-(methylthio)-benzothiazole moiety of BTS and the aromatic amino acid residue TRP108 of the lysozyme receptor. Next, conventional hydrogen bonding interactions contribute to the stability of the BTS-lysozyme coupling complex. In addition, mechanistic approaches performed using elastic network models revealed that the BTS ligand theoretically induces propagation of allosteric signals, suggesting non-physiological conformational flexing in large blocks of lysozyme affecting α-helices. Likewise, the BTS ligand interacts directly with allosteric residues, inducing perturbations in the conformational dynamics expressed as a moderate conformational softening in the α-helices H1, H2, and their corresponding β-loop in the lysozyme receptor, in contrast to the unbound state of lysozyme.

The In Vitro Antimicrobial and Antibiofilm Activities of Lysozyme against Gram-Positive Bacteria

“…The activities of LYS on biofilms are mediated by enzymatic targeting, and it significantly condenses the hydrophobicity of bacterial biofilms [16][17][18]. Besides, the biofilms of Enterococcus faecalis and Staphylococcus aureus are significantly inhibited at a high concentration of LYS (25 times of MICs) [18].…”

Advancements in application of chitosan and cyclodextrins in biomedicine and pharmaceutics: recent progress and future trends

“…Additional special molecules such as galactosyl and mannosyl can be attached to the chains of oligo(ethylene glycol) to enable recognition and targeting of specific cells. 124 …”

“… 119 Additionally, studies with β-CD, HP-β-CD, and per-6-amino-6-deoxy-β-CD improved aggregation. At the same time, it can inhibit the accumulation of various factors, such as branched-chain β-CD, 120 transgenic human growth factor, 121 basic fibroblast growth factor, 122 including glucosylglucosyl-β-CD (GUG-β-CyD), 122 insulin analogues, 123 and lysozyme in egg white 124 which are propagated by various molecules bearing aromatic amino acid residues. The ability of GUG-β-CD on TTR (tabulation of human transthyretin) amyloid formation was investigated.…”