Title
The reorganization of conformations, stability and aggregation of serum albumin isomers through the interaction of glycopeptide antibiotic teicoplanin: A thermodynamic and spectroscopy study
Author
Shivani A. Muthu, Helly Chetan Jadav, Sadhavi Srivastava, Raghuvir R. S. Pissurlenkar, Basir Ahmad
Year
2020
Journal
International Journal of Biological Macromolecules
Abstract
The drugs-protein binding study is of growing importance for drug-repurposing against amyloidosis. In this work, we study the binding of teicoplanin (TPN), a glycopeptide antibiotic, with bovine serum albumin (BSA) in its neutral (N), physiological (P) and basic (B) forms, which exist at pH 6, pH 7.4 and pH 9, respectively. The binding and thermodynamic parameters of TPN binding were determined by isothermal titration calorimetry (ITC) and fluorescence quench titration methods. Two binding sites were observed for N and P forms, whereas B form showed only one binding site. ITC and molecular docking results indicated that TPN-BSA complex formation is stabilized by hydrogen bonds, salt bridges and hydrophobic interaction. The red-edge excitation shift (REES) study indicated an ordered compact and spatial arrangement of the TPN bound protein molecule. TPN was found to affect the secondary and tertiary structures of B form only. The TPN binding was observed to marginally stabilize BSA isomers. TPN was also found to inhibit BSA aggregation as monitored by Rayleigh light scattering and thioflavin T binding assay. The current in vitro study will open a new path to explore the possible use of TPN as potential drugs to treat amyloidosis.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Tertiary structure, Biochemistry