Exploring the interaction between tyrphostin 9 and human serum albumin using biophysical and computational methods
Document Type
Article
Publication Date
9-21-2020
Abstract
Tyrphostin 9 (Tyr 9) is a potent platelet-derived growth factor receptor (PDGFR) inhibitor, which induces apoptosis in various cancer cell types. The binding of Tyr 9 to the major transport protein, human serum albumin (HSA) was investigated using several spectroscopic techniques and molecular docking method. Fluorescence quenching titration results showed progressive decrease in the protein fluorescence with increasing drug concentrations. A decreasing trend of the Stern-Volmer constant, K-sv with increasing temperature characterized the drug-induced quenching as static quenching, thus pointed towards the formation of Tyr 9?HSA complex. The binding constant of Tyr 9?HSA interaction was found to lie within the range 3.48?1.69???10(5) M-?1 at three different temperatures, i.e. 15 ?C, 25 ?C and 35??C, respectively and suggested intermediate binding affinity between Tyr 9 and HSA. The drug?HSA complex seems to be stabilized by hydrophobic forces, van der Waals forces and hydrogen bonds, as suggested from the thermodynamic data as well as molecular docking results. The far-UV and the near-UV CD spectral results showed slight alteration in the secondary and tertiary structures, respectively, of the protein upon Tyr 9 binding. Interaction of Tyr 9 with HSA also produced microenvironmental perturbations around protein fluorophores, as evident from the three-dimensional fluorescence spectral results but increased protein?s thermal stability. Both competitive drug binding results and molecular docking analysis suggested Sudlow?s Site I of HSA as the preferred Tyr 9 binding site. Communicated by Ramaswamy H. Sarma
Keywords
Tyrphostin 9, Human serum albumin, Fluorescence quenching, Drug?protein interaction, Molecular docking
Divisions
InstituteofBiologicalSciences
Funders
Universiti Malaya (FG025-17AFR)
Publication Title
Journal of Biomolecular Structure and Dynamics
Volume
38
Issue
14
Publisher
Taylor & Francis
Publisher Location
530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA