α1-antitrypsin (A1AT) is a circulating serine protease inhibitor and an acute phase reactant, the deficiency of which can lead to liver failure and chronic lung disease. Flavonoid treatment may induce changes in α1-antitrypsin production in some human cells. The purpose of this study is to investigate the properties of the A1AT protein that interacts with the flavonoid luteolin, which exhibits numerous properties, including antioxidant properties. For this purpose, multi-spectroscopic (UV-Vis spectroscopy, fluorescence and FRET) methods and molecular docking were used. The intrinsic fluorescence of A1AT was quenched by luteolin through a static mechanism. Luteolin binds to one site of the A1AT protein, with a moderate binding constant, and the binding process was driven by entropy and hydrophobic interactions. Hydrophobicity around Trp decreased as a result of luteolin binding to the A1AT site and FRET occurred at a distance of 3.11 nm. Under the action of temperature, the stability of A1AT structure was decreased by the presence of luteolin. Molecular docking confirmed that luteolin binds to one site, with a moderate affinity. The results would give a better understanding of the functional changes that occurred in the structure of A1AT induced by luteolin binding, which may have implications in the field of pharmaceutical research.Communicated by Ramaswamy H. Sarma.
Keywords: binding mechanism; luteolin; structure stability; α1-antitrypsin.