Exploring the interaction between tyrphostin 9 and human serum albumin using biophysical and computational methods.
J Biomol Struct Dyn
; 38(14): 4134-4142, 2020 Sep.
Article
en En
| MEDLINE
| ID: mdl-31552810
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 × 105 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Albúmina Sérica Humana
Límite:
Humans
Idioma:
En
Revista:
J Biomol Struct Dyn
Año:
2020
Tipo del documento:
Article
País de afiliación:
Malasia